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Fine particulate air pollution <2.5 μm in diameter (PM(2.5)) is a major environmental threat to global public health. Multiple national and international medical and governmental organizations have recognized PM(2.5) as a risk factor for cardiopulmonary diseases. A growing body of evidence indicates that several personal-level approaches that reduce exposures to PM(2.5) can lead to improvements in health endpoints. Novel and forward-thinking strategies including randomized clinical trials are important to validate key aspects (e.g., feasibility, efficacy, health benefits, risks, burden, costs) of the various protective interventions, in particular among real-world susceptible and vulnerable populations. This paper summarizes the discussions and conclusions from an expert workshop, Reducing the Cardiopulmonary Impact of Particulate Matter Air Pollution in High Risk Populations, held on May 29 to 30, 2019, and convened by the National Institutes of Health, the U.S. Environmental Protection Agency, and the U.S. Centers for Disease Control and Prevention.

En el marco del proyecto de investigaci?n colaborativo ?La informaci?n gen?tica en salud: algunos aspectos ?ticos y jur?dicos?, se invit? a los investigadores a distintos pa?ses de Latinoam?rica a que brindaran informaci?n acerca de la regulaci?n sobre bancos de datos gen?ticos y realizaci?n deestudios gen?ticos en sus respectivos pa?ses. ; Within the framework of the collaborative research project "Genetic information in health: some ethical and legal aspects", researchers from different Latin American countries were invited to provide information on the regulation of genetic data banks and genetic studies in their respective countries. ; Rionegro

On New Shores focuses on immigrant fathers in North America and provides readers with a richer and more comprehensive approach to how researchers, practitioners, and social policymakers can examine immigrant fathering among ethnic minority families. The chapters focus on the various methodological advances used to explicitly investigate immigrant fathers

Background The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2.5th percentile estimated between 1990 and 2030, and 100 as the 97.5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings Globally, the median health-related SDG index was 56.7 (IQR 31.9-66.8) in 2016 and country-level performance markedly varied, with Singapore (86.8, 95% uncertainty interval 84.6-88.9), Iceland (86.0, 84.1-87.6), and Sweden (85.6, 81.8-87.8) having the highest levels in 2016 and Afghanistan (10.9, 9.6-11.9), the Central African Republic (11.0, 8.8-13.8), and Somalia (11.3, 9.5-13.1) recording the lowest. Between 2000 and 2016, notable improvements in the UHC index were achieved by several countries, including Cambodia, Rwanda, Equatorial Guinea, Laos, Turkey, and China; however, a number of countries, such as Lesotho and the Central African Republic, but also high-income countries, such as the USA, showed minimal gains. Based on projections of past trends, the median number of SDG targets attained in 2030 was five (IQR 2-8) of the 24 defined targets currently measured. Globally, projected target attainment considerably varied by SDG indicator, ranging from more than 60% of countries projected to reach targets for under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria, to less than 5% of countries projected to achieve targets linked to 11 indicator targets, including those for childhood overweight, tuberculosis, and road injury mortality. For several of the health-related SDGs, meeting defined targets hinges upon substantially faster progress than what most countries have achieved in the past. Interpretation GBD 2016 provides an updated and expanded evidence base on where the world currently stands in terms of the health-related SDGs. Our improved measure of UHC offers a basis to monitor the expansion of health services necessary to meet the SDGs. Based on past rates of progress, many places are facing challenges in meeting defined health-related SDG targets, particularly among countries that are the worst off. In view of the early stages of SDG implementation, however, opportunity remains to take actions to accelerate progress, as shown by the catalytic effects of adopting the Millennium Development Goals after 2000. With the SDGs' broader, bolder development agenda, multisectoral commitments and investments are vital to make the health-related SDGs within reach of all populations. Copyright The Authors. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 4.0 license. ; Peer reviewed

Background The UN's Sustainable Development Goals (SDGs) are grounded in the global ambition of "leaving no one behind". Understanding today's gains and gaps for the health-related SDGs is essential for decision makers as they aim to improve the health of populations. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016), we measured 37 of the 50 health-related SDG indicators over the period 1990-2016 for 188 countries, and then on the basis of these past trends, we projected indicators to 2030. Methods We used standardised GBD 2016 methods to measure 37 health-related indicators from 1990 to 2016, an increase of four indicators since GBD 2015. We substantially revised the universal health coverage (UHC) measure, which focuses on coverage of essential health services, to also represent personal health-care access and quality for several non-communicable diseases. We transformed each indicator on a scale of 0-100, with 0 as the 2.5th percentile estimated between 1990 and 2030, and 100 as the 97.5th percentile during that time. An index representing all 37 health-related SDG indicators was constructed by taking the geometric mean of scaled indicators by target. On the basis of past trends, we produced projections of indicator values, using a weighted average of the indicator and country-specific annualised rates of change from 1990 to 2016 with weights for each annual rate of change based on out-of-sample validity. 24 of the currently measured health-related SDG indicators have defined SDG targets, against which we assessed attainment. Findings Globally, the median health-related SDG index was 56.7 (IQR 31.9-66.8) in 2016 and country-level performance markedly varied, with Singapore (86.8, 95% uncertainty interval 84.6-88.9), Iceland (86.0, 84.1-87.6), and Sweden (85.6, 81.8-87.8) having the highest levels in 2016 and Afghanistan (10.9, 9.6-11.9), the Central African Republic (11.0, 8.8-13.8), and Somalia (11.3, 9.5-13.1) recording the lowest. Between 2000 and 2016, notable ...

Si listano le singole sezioni in cui S.Simoncelli ha contribuito. Ogni sezione puo' essere citata separatamente dal report 1.1 Ocean temperature and salinity S. Mulet, B. Buongiorno Nardelli, S. Good, A. Pisano, E. Greiner, M. Monier E. Autret, L. Axell, F. Boberg, S. Ciliberti, M. Drévillon, R. Droghei, O. Embury, J. Gourrion, J. Høyer, M. Juza, J. Kennedy, B. Lemieux-Dudon, E. Peneva, R. Reid, S. Simoncelli, A. Storto, J. Tinker, K. von Schuckmann, S. L. Wakelin. 2.1. Ocean heat content .K. von Schuckmann, A. Storto, S. Simoncelli, R. P. Raj, A.Samuelsen, A. de Pascual Collar, M. Garcia Sotillo, T Szerkely, M. Mayer, K. A. Peterson, H. Zuo, G. Garric, M. Monier. 3.4 Water mass formation processes in the Mediterranean Sea over the past 30 years S. Simoncelli, Nadia Pinardi, C. Fratianni, C. Dubois, G. Notarstefano. 3.5 Ventilation of the Western Mediterranean Deep Water through the Strait of Gibraltar S. Sammartino, J. García Lafuente, C. Naranjo, S. Simoncelli. 4.4 Unusual salinity pattern in the South Adriatic Sea in 2016 Z. Kokkini, G. Notarstefano P-M Poulain, E. Mauri, R. Gerin, S. Simoncelli ; The oceans regulate our weather and climate from global to regional scales. They absorb over 90% of accumulated heat in the climate system (IPCC 2013 IPCC. 2013. Climate change 2013: The physical science basis. Contribution of working group I to the fifth assessment report of the intergovernmental panel on climate change [Stocker TF, Qin D, Plattner G-K, Tignor M, Allen SK, Boschung J, Nauels A, Xia Y, Bex V, Midgley PM, editors]. Cambridge: Cambridge University Press, 1535. doi:10.1017/CBO9781107415324. [Crossref], , [Google Scholar]) and over a quarter of the anthropogenic carbon dioxide (Le Quéré et al. 2016 Le Quéré C, Andrew RM, Canadell JG, Sitch S, Korsbakken JI, Peters GP, Manning AC, Boden TA, Tans PP, Houghton RA, et al. 2016. Global carbon budget 2016. Earth Syst Sci Data. 8( 2): 605– 649. doi:10.5194/essd-8-605-2016 [Crossref], [Web of Science ®], , [Google Scholar]). They provide nearly half of the world's oxygen. Most of our rain and drinking water is ultimately regulated by the sea. The oceans provide food and energy and are an important source of the planet's biodiversity and ecosystem services. They are vital conduits for trade and transportation and many economic activities depend on them (OECD 2016 OECD . 2016. The ocean economy in 2030. Paris : OECD Publishing. doi:10.1787/9789264251724-en. [Crossref], , [Google Scholar]). Our oceans are, however, under threat due to climate change and other human induced activities and it is vital to develop much better, sustainable and science-based reporting and management approaches (UN 2017 UN . 2017. Report of the United Nations conference to support the implementation of sustainable development goal 14: Conserve and sustainably use the oceans, seas and marine resources for sustainable development (Advance unedited version). https://sustainabledevelopment.un.org/content/documents/15662FINAL_15_June_2017_RepoRe_Goal_14.pdf . [Google Scholar]). Better management of our oceans requires long-term, continuous and state-of-the art monitoring of the oceans from physics to ecosystems and global to local scales. The Copernicus Marine Environment Monitoring Service (CMEMS) has been set up to address these challenges at European level. Mercator Ocean was tasked in 2014 by the European Union under a delegation agreement to implement the operational phase of the service from 2015 to 2021 (CMEMS 2014 CMEMS . 2014. Technical annex to the delegation agreement with Mercator Ocean for the implementation of the Copernicus Marine Environment Monitoring Service (CMEMS). www.copernicus.eu/sites/default/files/library/CMEM_TechnicalAnnex_PUBLIC.docx.pdf . [Google Scholar]). The CMEMS now provides regular and systematic reference information on the physical state, variability and dynamics of the ocean, ice and marine ecosystems for the global ocean and the European regional seas (Figure 0.1; CMEMS 2016 CMEMS . 2016. High level service evolution strategy, a document prepared by Mercator Ocean with the support of the CMEMS STAC. [Google Scholar]). This capacity encompasses the description of the current situation (analysis), the prediction of the situation 10 days ahead (forecast), and the provision of consistent retrospective data records for recent years (reprocessing and reanalysis). CMEMS provides a sustainable response to European user needs in four areas of benefits: (i) maritime safety, (ii) marine resources, (iii) coastal and marine environment and (iv) weather, seasonal forecast and climate. ; Copernicus Marine Environment Monitoring Service ; Published ; S1-S142 ; 4A. Oceanografia e clima ; JCR Journal

RESUMEN: Este libro se puede leer en muchos niveles. Uno de ellos puede no ser muy obvio para aquellos que están acostumbrados a leer sobre violencia e inseguridad en América Latina. Es el nivel que le da a este libro un estatus de originalidad y una contribución que va más allá de la región: el ser una forma de conocimiento destinada no solo a interpretar el mundo, sino a cambiarlo […], visibiliza la importancia de un proceso de investigación ajustado al tipo de conocimiento que produce. Aquí se conectan el proceso y el resultado, lo que debería propiciar un debate más amplio con respecto a cómo y qué sabemos de la naturaleza de la violencia y la agencia social para reducirla […]. Esta visión es particularmente relevante en contextos donde el Estado reproduce la violencia, con terribles impactos, en especial en periferias excluidas. […] El proceso de investigación abordado en este libro transgredió muchas fronteras. Hubo fronteras entre países, barreras lingüísticas, fronteras en torno a la educación, el conocimiento y la experiencia, y entre etnias, géneros y generaciones. […] este proceso reunió a académicos, activistas y líderes comunitarios de cinco países de América Latina y uno del Caribe, incluyendo comunidades indígenas en México y Guatemala […]. La violencia está en el tiempo y en el espacio y se reproduce entre las generaciones en diversos espacios de socialización. Este proceso de investigación que trasciende las fronteras, plantea una discusión que atraviesa los diferentes casos sobre cómo los déficits y las desigualdades materiales, las violencias estatales en nombre de la 'seguridad', las especificidades culturales, de género y generacionales de la experiencia y la comprensión de la violencia, así como las diversas formas de criminalidad, se cruzan y se reproducen a través del tiempo y el espacio. Jenny Pearce, investigadora y profesora en el Latin American and Caribbean Centre (LACC) de la London School of Economics and Political Science ; ABSTRACT: This book can be read on many levels. One level may not be so obvious to those who are used to reading about violence and insecurity in Latin America. It is the level which gives this book a claim to true originality and a contribution beyond the region. This contribution is to form of scholarship aimed not only to interpret the world but to change it […], this text visibilizes the significance of the research process to the kind of knowledge that is produced. It connects process and outcome, and this should start a wider debate about how as well as what we know about the nature of violence and the social agency to reduce it […]. This is particularly relevant in contexts where the State reproduces violence, with terrible impacts on the margins. The research process discussed in this book transgressed many boundaries. There were intercountry borders, linguistic barriers, boundaries around education, knowledge and experience and between ethnicities, genders and generations. […] the research process brought together scholars and community activists and actors from five Latin American and one Caribbean country. And within Latin America there were indigenous communities in Mexico and Guatemala who participated […]. Violence is located in time and space. It is reproduced inter-generationally through varied socialisation spaces. The boundary crossing research process, raises cross case discussion about how material deficits and inequalities, state violences in the name of 'security', cultural, gender and generational specificities of experience and understanding of violence, and varied forms of criminality, intersect and reproduce through time and space. Professor Jenny Pearce. Latin American and Caribbean Centre (LACC), London School of Economics and Political Science

COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani 1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT ; COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Cédric Bosteels33, Ahmed A. Bousfiha34, Claire Bouvattier35, Oksana Boyarchuk36, Maria Rita P. Bueno37, Jacinta Bustamante20, Juan José Cáceres Agra38, Semra Calimli39, Ruggero Capra40, Maria Carrabba41, Carlos Casasnovas42, Marion Caseris43, Martin Castelle44, Francesco Castelli45, Martín Castillo de Vera46, Mateus V. Castro37, Emilie Catherinot47, Martin Chalumeau48, Bruno Charbit49, Matthew P. Cheng50, Père Clavé31, Bonaventura Clotet51, Anna Codina52, Fatih Colkesen53, Fatma Çölkesen54, Roger Colobran55, Cloé Comarmond56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Jean-Luc Diehl65, Stephanie Dobbelaere66, Sophie Durand67, Waleed Eldars68, Mohamed Elgamal69, Marwa H. Elnagdy70, Melike Emiroglu71, Emine Hafize Erdeniz72, Selma Erol Aytekin73, Romain Euvrard74, Recep Evcen75, Giovanna Fabio41, Laurence Faivre76, Antonin Falck43, Muriel Fartoukh77, Morgane Faure78, Miguel Fernandez Arquero79, Carlos Flores80, Bruno Francois81, Victoria Fumadó82, Francesca Fusco83, Blanca Garcia Solis84, Pascale Gaussem85, Juana Gil-Herrera86, Laurent Gilardin87, Monica Girona Alarcon88, Mònica Girona-Alarcón88, Jean-Christophe Goffard89, Funda Gok90, Rafaela González-Montelongo91, Antoine Guerder92, Yahya Gul93, Sukru Nail Guner93, Marta Gut94, Jérôme Hadjadj95, Filomeen Haerynck96, Rabih Halwani97, Lennart Hammarström98, Nevin Hatipoglu99, Elisa Hernandez-Brito100, Cathérine Heijmans101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Levi Hoste104, Eric Hoste105, Sami Hraiech106, Linda Humbert107, Alejandro D. Iglesias108, Antonio Íñigo-Campos91, Matthieu Jamme109, María Jesús Arranz110, Iolanda Jordan111, Philippe Jorens112, Fikret Kanat113, Hasan Kapakli114, Iskender Kara115, Adem Karbuz116, Kadriye Kart Yasar117, Sevgi Keles118, Yasemin Kendir Demirkol119, Adam Klocperk120, Zbigniew J. Król121, Paul Kuentz122, Yat Wah M. Kwan123, Jean-Christophe Lagier124, Bart N. Lambrecht33, Yu-Lung Lau125, Fleur Le Bourgeois60, Yee-Sin Leo126, Rafael Leon Lopez127, Daniel Leung125, Michael Levin128, Michael Levy60, Romain Lévy20, Zhi Li49, Agnes Linglart129, Bart Loeys130, José M. Lorenzo-Salazar91, Céline Louapre131, Catherine Lubetzki131, Charles-Edouard Luyt132, David C. Lye133, Davood Mansouri134, Majid Marjani135, Jesus Marquez Pereira136, Andrea Martin137, David Martínez Pueyo138, Javier Martinez-Picado139, Iciar Marzana140, Alexis Mathian14, Larissa R. B. Matos37, Gail V. Matthews141, Julien Mayaux142, Jean-Louis Mège143, Isabelle Melki144, Jean-François Meritet145, Ozge Metin146, Isabelle Meyts147, Mehdi Mezidi148, Isabelle Migeotte149, Maude Millereux150, Tristan Mirault151, Clotilde Mircher67, Mehdi Mirsaeidi152, Abián Montesdeoca Melián153, Antonio Morales Martinez154, Pierre Morange155, Clémence Mordacq107, Guillaume Morelle156, Stéphane Mouly13, Adrián Muñoz-Barrera91, Leslie Naesens157, Cyril Nafati158, João Farela Neves159, Lisa FP. Ng160, Yeray Novoa Medina161, Esmeralda Nuñez Cuadros162, J. Gonzalo Ocejo-Vinyals163, Zerrin Orbak164, Mehdi Oualha20, Tayfun Özçelik165, Qiang Pan-Hammarström166, Christophe Parizot142, Tiffany Pascreau167, Estela Paz-Artal168, Sandra Pellegrini49, Rebeca Pérez de Diego84, Aurélien Philippe169, Quentin Philippot77, Laura Planas-Serra170, Dominique Ploin171, Julien Poissy172, Géraldine Poncelet43, Marie Pouletty173, Paul Quentric142, Didier Raoult143, Anne-Sophie Rebillat67, Ismail Reisli174, Pilar Ricart175, Jean-Christophe Richard176, Nadia Rivet28, Jacques G. Rivière177, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego178, Agustí Rodríguez-Palmero179, Carolina Soledad Romero180, Anya Rothenbuhler181, Flore Rozenberg182, Maria Yolanda Ruiz del Prado183, Joan Sabater Riera15, Oliver Sanchez184, Silvia Sánchez-Ramón185, Agatha Schluter170, Matthieu Schmidt186, Cyril E. Schweitzer187, Francesco Scolari188, Anna Sediva189, Luis M. Seijo190, Damien Sene13, Sevtap Senoglu117, Mikko R. J. Seppänen191, Alex Serra Ilovich192, Mohammad Shahrooei62, Hans Slabbynck193, David M. Smadja194, Ali Sobh195, Xavier Solanich Moreno15, Jordi Solé-Violán196, Catherine Soler197, Pere Soler-Palacín137, Yuri Stepanovskiy198, Annabelle Stoclin199, Fabio Taccone149, Yacine Tandjaoui-Lambiotte200, Jean-Luc Taupin201, Simon J. Tavernier202, Benjamin Terrier203, Caroline Thumerelle107, Gabriele Tomasoni204, Julie Toubiana48, Josep Trenado Alvarez205, Sophie Trouillet-Assant206, Jesús Troya207, Alessandra Tucci208, Matilde Valeria Ursini‬83, Yurdagul Uzunhan209, Pierre Vabres210, Juan Valencia-Ramos211, Eva Van Braeckel33, Stijn Van de Velde212, Ana Maria Van Den Rym84, Jens Van Praet213, Isabelle Vandernoot214, Hulya Vatansev215, Valentina Vélez-Santamaria42, Sébastien Viel171, Cédric Vilain216, Marie E. Vilaire67, Audrey Vincent35, Guillaume Voiriot217, Fanny Vuotto107, Alper Yosunkaya90, Barnaby E. Young126, Fatih Yucel218, Faiez Zannad219, Mayana Zatz37, Alexandre Belot220* ; Imagine COVID Group Christine Bole-Feysot, Stanislas Lyonnet*, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID Group. ; French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric D'Ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent VE Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Trioux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases Initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, Paris, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22CHU Rouen–SMIT, Rouen, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d'Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28CHU de Bordeaux–SMIT, Bordeaux, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Hôpital Louis Mourier–Gynécologie, Colombes, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35Hôpital la Timone, Marseille, France. 36Bichat–SMIT, Paris, France. ; CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cadiergues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d'Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M'Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children's Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris, France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France. 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, Bordeaux, France. 16Hôpital Hotel Dieu, APHP, Paris, France. 17Service des Explorations Fonctionnelles, Hôpital Bichat–Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France. ; Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve de Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P.J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek4* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC Consortium. ; COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Alessia David21, Joseph L. DeRisi22, Murkesh Desai23, Beth A. Drolet24, Sara Espinosa25, Jacques Fellay26, Carlos Flores27, Jose Luis Franco28, Peter K. Gregersen29, Filomeen Haerynck30, David Hagin31, Rabih Halwani32, Jim Heath33, Sarah E. Henrickson34, Elena Hsieh35, Kohsuke Imai36, Yuval Itan8, Timokratis Karamitros37, Kai Kisand38, Cheng-Lung Ku39, Yu-Lung Lau40, Yun Ling41, Carrie L. Lucas42, Tom Maniatis43, Davoud Mansouri44, Laszlo Marodi45, Isabelle Meyts46, Joshua Milner47, Kristina Mironska48, Trine Mogensen49, Tomohiro Morio50, Lisa FP. Ng51, Luigi D. Notarangelo52, Antonio Novelli53, Giuseppe Novelli54, Cliona O'Farrelly55, Satoshi Okada56, Tayfun Ozcelik57, Rebeca Perez de Diego58, Anna M. Planas59, Carolina Prando60, Aurora Pujol61, Lluis Quintana-Murci62, Laurent Renia63, Alessandra Renieri64, Carlos Rodríguez-Gallego65, Vanessa Sancho-Shimizu66, Vijay Sankaran67, Kelly Schiabor Barrett9, Mohammed Shahrooei68, Andrew Snow69, Pere Soler-Palacín70, András N. Spaan71, Stuart Tangye72, Stuart Turvey73, Furkan Uddin74, Mohammed J. Uddin75, Diederik van de Beek76, Sara E. Vazquez77, Donald C. Vinh78, Horst von Bernuth79, Nicole Washington9, Pawel Zawadzki80, Helen C. Su52, Jean-Laurent Casanova81 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Departement, Faculty of Medicine and Pharmacy, Averroes University Hospital; LICIA Laboratoire d'Immunologie Clinique, d'Inflammation et d'Allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory University Department of Pediatrics and Children's Healthcare of Atlanta, Atlanta, GA, USA. 17Murdoch Children's Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21Centre for Bioinformatics and System Biology, Department of Life Sciences, Imperial College London, South Kensington Campus, London, UK. 22University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. 23Bai Jerbai Wadia Hospital for Children, Mumbai, India. 24School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 25Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 26Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 27Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 28University of Antioquia, Medellín, Colombia. 29Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 30Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 31The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 32Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 33Institute for Systems Biology, Seattle, WA, USA. 34Children's Hospital of Philadelphia, Philadelphia, PA, USA. 35Anschutz Medical Campus, Aurora, CO, USA. 36Riken, Tokyo, Japan. 37Hellenic Pasteur Institute, Athens, Greece. 38University of Tartu, Tartu, Estonia. 39Chang Gung University, Taoyuan County, Taiwan. 40The University of Hong Kong, Hong Kong, China. 41Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 42Yale School of Medicine, New Haven, CT, USA. 43New York Genome Center, New York, NY, USA. 44Shahid Beheshti University of Medical Sciences, Tehran, Iran. 45Semmelweis University Budapest, Budapest, Hungary. 46KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 47Columbia University Medical Center, New York, NY, USA. 48University Clinic for Children's Diseases, Skopje, North Macedonia. 49Aarhus University, Aarhus, Denmark. 50Tokyo Medical & Dental University Hospital, Tokyo, Japan. 51Singapore Immunology Network, Singapore. 52National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 53Bambino Gesù Children's Hospital, Rome, Italy. 54Department of Biomedicine and Prevention, University of Rome "Tor Vergata," Rome, Italy. 55Trinity College, Dublin, Ireland. 56Hiroshima University, Hiroshima, Japan. 57Bilkent University, Ankara, Turkey. 58Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 59IIBB-CSIC, IDIBAPS, Barcelona, Spain. 60Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 61Neurometabolic Diseases Laboratory, IDIBELL–Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 62Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 63Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 64Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Italy; GEN-COVID Multicenter Study. 65Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Canary Islands, Spain. 66Imperial College London, London, UK. 67Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 68Saeed Pathobiology and Genetic Lab, Tehran, Iran. 69Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 70Hospital Universitari Vall d'Hebron, Barcelona, Spain. 71University Medical Center Utrecht, Amsterdam, The Netherlands. 72Garvan Institute of Medical Research, Sydney, Australia. 73The University of British Columbia, Vancouver, Canada. 74Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children's Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children's Healthcare, Dhaka, Bangladesh. 75Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 76Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, The Netherlands. 77University of California, San Francisco, CA, USA. 78McGill University Health Centre, Montreal, Canada. 79Charité–Berlin University Hospital Center, Berlin, Germany. 80Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 81Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort. ; NIAID-USUHS/TAGC COVID Immunity Group Huie Jing1,2, Wesley Tung1,2, Christopher R. Luthers3, Bradly M. Bauman3, Samantha Shafer2,4, Lixin Zheng2,4, Zinan Zhang2,4, Satoshi Kubo2,4, Samuel D. Chauvin2,4, Kazuyuki Meguro1,2, Elana Shaw1,2, Michael Lenardo2,4, Justin Lack5, Eric Karlins6, Daniel M. Hupalo7, John Rosenberger7, Gauthaman Sukumar7, Matthew D. Wilkerson7, Xijun Zhang7 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD, USA. 3Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 4Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 5NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. 6Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 7The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. ; Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection. ; We thank the generous donation from Fisher Center for Alzheimer's Research Foundation for our research. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the "Investments for the Future" program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l'enfance, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Paris. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). Regione Lombardia, Italy (project "Risposta immune in pazienti con COVID-19 e co-morbidità"), and the Intramural Research Program of the NIAID, NIH. The laboratory of Genomes & Cell Biology of Disease is supported by "Integrative Biology of Emerging Infectious Diseases" (grant no. ANR-10-LABX-62-IBEID), the "Fondation pour la Recherche Medicale" (grant FRM - EQU202003010193), the "Agence Nationale de la Recherche" (ANR FLASH COVID project IDISCOVR cofounded by the "Fondation pour la Recherche Médicale"), University of Paris ("Plan de Soutien Covid-19": RACPL20FIR01-COVID-SOUL). IM is a senior clinical investigator with the FWO Vlaanderen; IM and LM are supported by FWO G0C8517N – GOB5120N. The VS team was supported by "Agence Nationale de la Recherche" (ANR-17-CE15-0003, ANR-17-CE15-0003-01), and by Université de Paris "PLAN D'URGENCE COVID19". LK was supported by a fellowship from the French Ministry of Research. VS-S is supported by a UKRI Future Leaders Fellowship (MR/S032304/1). SZA-M is supported by the Elite Journals Program at King Saud University through grant number PEJP-16-107. JM lab is supported by Columbia University COVID biobank and grant: UL1TR001873. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. JLP is supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). Work at the Neurometabolic Diseases Laboratory received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 824110 (EasiGenomics grant COVID-19/ PID12342) to A.P., and Roche and Illumina Covid Match Funds to M.G. C.R.G and colleagues are supported by cInstituto de Salud Carlos III (COV20_01333 and COV20_01334), Spanish Ministry of Science and Innovation, with the funding of European Regional Development Fund-European Social Fund -FEDER-FSE; (RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and "Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19"). D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. Helen Su is adjunct faculty at the University of Pennsylvania. A-L.N. was supported by the Foundation Bettencourt Schueller. The Amsterdam UMC Covid-19 Biobank was funded by the Netherlands Organization for Health Research and Development (ZonMw, NWO-vici 91819627), The Corona Research Fund (Amsterdam UMC), Dr. J. C. Vaillantfonds, and Amsterdam UMC. Work on COVID-19 at the AG-S lab is partly supported by NIH supplements to grants U19AI135972, U19AI142733 and R35 HL135834, and to contract HHSN272201800048C, by a DoD supplement to grant W81XWH-20-1-0270, by DARPA project HR0011-19-2-0020, by CRIP (Center for Research on Influenza Pathogenesis), a NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400008C), by an NIAID funded Collaborative Influenza Vaccine Innovation Center (SEM-CIVIC, contract 75N93019C00051) and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611(5384)) and anonymous donors. The Virscan analysis presented in fig. S11 was performed with financial support from Sidra Medicine ; Peer reviewed

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10-8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. ; BCAC acknowledgements. We thank all the individuals who took part in these studies and all the researchers, clinicians, technicians and administrative staff who have enabled this work to be carried out. ABCFS thank Maggie Angelakos, Judi Maskiell, Gillian Dite. ABCS thanks the Blood bank Sanquin, The Netherlands. ABCTB Investigators: Christine Clarke, Deborah Marsh, Rodney Scott, Robert Baxter, Desmond Yip, Jane Carpenter, Alison Davis, Nirmala Pathmanathan, Peter Simpson, J. Dinny Graham, Mythily Sachchithananthan. Samples are made available to researchers on a non-exclusive basis. BBCS thanks Eileen Williams, Elaine Ryder-Mills, Kara Sargus. BCEES thanks Allyson Thomson, Christobel Saunders, Terry Slevin, BreastScreen Western Australia, Elizabeth Wylie, Rachel Lloyd. The BCINIS study would not have been possible without the contributions of Dr. K. Landsman, Dr. N. Gronich, Dr. A. Flugelman, Dr. W. Saliba, Dr. E. Liani, Dr. I. Cohen, Dr. S. Kalet, Dr. V. Friedman, Dr. O. Barnet of the NICCC in Haifa, and all the contributing family medicine, surgery, pathology and oncology teams in all medical institutes in Northern Israel. The BREOGAN study would not have been possible without the contributions of the following: Manuela Gago-Dominguez, Jose Esteban Castelao, Angel Carracedo, Victor Munoz Garzon, Alejandro Novo Dominguez, Maria Elena Martinez, Sara Miranda Ponte, Carmen Redondo Marey, Maite Pena Fernandez, Manuel Enguix Castelo, Maria Torres, Manuel Calaza (BREOGAN), Jose Antunez, Maximo Fraga and the staff of the Department of Pathology and Biobank of the University Hospital Complex of Santiago-CHUS, Instituto de Investigacion Sanitaria de Santiago, IDIS, Xerencia de Xestion Integrada de Santiago-SERGAS; Joaquin Gonzalez-Carrero and the staff of the Department of Pathology and Biobank of University Hospital Complex of Vigo, Instituto de Investigacion Biomedica Galicia Sur, SERGAS, Vigo, Spain. BSUCH thanks Peter Bugert, Medical Faculty Mannheim. CBCS thanks study participants, co-investigators, collaborators and staff of the Canadian Breast Cancer Study, and project coordinators Agnes Lai and Celine Morissette. CCGP thanks Styliani Apostolaki, Anna Margiolaki, Georgios Nintos, Maria Perraki, Georgia Saloustrou, Georgia Sevastaki, Konstantinos Pompodakis. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgard Hansen. The Danish Cancer Biobank is acknowledged for providing infrastructure for the collection of blood samples for the cases. CNIO-BCS thanks Guillermo Pita, Charo Alonso, Nuria alvarez, Pilar Zamora, Primitiva Menendez, the Human Genotyping-CEGEN Unit (CNIO). The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, and Eunjung Lee at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine, and Fred Schumacher at Case Western University. DIETCOMPLYF thanks the patients, nurses and clinical staff involved in the study. The DietCompLyf study was funded by the charity Against Breast Cancer (Registered Charity Number 1121258) and the NCRN. We thank the participants and the investigators of EPIC (European Prospective Investigation into Cancer and Nutrition). ESTHER thanks Hartwig Ziegler, Sonja Wolf, Volker Hermann, Christa Stegmaier, Katja Butterbach. GC-HBOC thanks Stefanie Engert, Heide Hellebrand, Sandra Krober and LIFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nuchter, Ronny Baber). The GENICA Network: Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tubingen, Germany [HB, Wing-Yee Lo], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site Tubingen [[HB], gefordert durch die Deutsche Forschungsgemeinschaft (DFG) im Rahmen der Exzellenzstrategie des Bundes und der Lander - EXC 2180 - 390900677 [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [YDK, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [Thomas Bruning, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]. HABCS thanks Michael Bremer. HEBCS thanks Kirsimari Aaltonen, Irja Erkkila. HUBCS thanks Shamil Gantsev. KARMA and SASBAC thank the Swedish Medical Research Counsel. KBCP thanks Eija Myohanen, Helena Kemilainen. kConFab/AOCS wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow-Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. LMBC thanks Gilian Peuteman, Thomas Van Brussel, EvyVanderheyden and Kathleen Corthouts. MARIE thanks Petra Seibold, Dieter Flesch-Janys, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. MBCSG (Milan Breast Cancer Study Group): Mariarosaria Calvello, Davide Bondavalli, Aliana Guerrieri Gonzaga, Monica Marabelli, Irene Feroce, and the personnel of the Cogentech Cancer Genetic Test Laboratory. The MCCS was made possible by the contribution of many people, including the original investigators, the teams that recruited the participants and continue working on follow-up, and the many thousands of Melbourne residents who continue to participate in the study. We thank the coordinators, the research staff and especially the MMHS participants for their continued collaboration on research studies in breast cancer. MSKCC thanks Marina Corines, Lauren Jacobs. MTLGEBCS would like to thank Martine Tranchant (CHU de Quebec - Universite Laval Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill University) for DNA extraction, sample management and skilful technical assistance. J.S. is Chair holder of the Canada Research Chair in Oncogenetics. NBHS and SBCGS thank study participants and research staff for their contributions and commitment to the studies. For NHS and NHS2 the study protocol was approved by the institutional review boards of the Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. We would like to thank the participants and staff of the NHS and NHS2 for their valuable contributions as well as the following state cancer registries for their help: A.L., A.Z., A.R., C.A., C.O., C.T., D.E., F.L., G.A., I.D., I.L., I.N., I.A., K.Y., L.A., M.E., M.D., M.A., M.I., N.E., N.H., N.J., N.Y., N.C., N.D., O.H., O.K., O.R., P.A., R.I., S.C., T.N., T.X., V.A., W.A., and W.Y. The authors assume full responsibility for analyses and interpretation of these data. OFBCR thanks Teresa Selander, Nayana Weerasooriya. ORIGO thanks E. Krol-Warmerdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. PBCS thanks Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao, Michael Stagner. The ethical approval for the POSH study is MREC /00/6/69, UKCRN ID: 1137. We thank staff in the Experimental Cancer Medicine Centre (ECMC) supported Faculty of Medicine Tissue Bank and the Faculty of Medicine DNA Banking resource. RBCS thanks Jannet Blom, Saskia Pelders, Annette Heemskerk and the Erasmus MC Family Cancer Clinic. We thank the SEARCH and EPIC teams. SKKDKFZS thanks all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. SZBCS thanks Ewa Putresza. UCIBCS thanks Irene Masunaka. UKBGS thanks Breast Cancer Now and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. We acknowledge funding to the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). The authors thank the WHI investigators and staff for their dedication and the study participants for making the program possible. CIMBA acknowledgments. All the families and clinicians who contribute to the studies; Catherine M. Phelan for her contribution to CIMBA until she passed away on 22 September 2017; Sue Healey, in particular taking on the task of mutation classification with the late Olga Sinilnikova; Maggie Angelakos, Judi Maskiell, Gillian Dite, Helen Tsimiklis; members and participants in the New York site of the Breast Cancer Family Registry; members and participants in the Ontario Familial Breast Cancer Registry; Vilius Rudaitis and Laimonas Grikeviius; Drs Janis Eglitis, Anna Krilova and Aivars Stengrevics; Yuan Chun Ding and Linda Steele for their work in participant enrollment and biospecimen and data management; Bent Ejlertsen and Anne-Marie Gerdes for the recruitment and genetic counseling of participants; Alicia Barroso, Rosario Alonso and Guillermo Pita; all the individuals and the researchers who took part in CONSIT TEAM (Consorzio Italiano Tumori Ereditari Alla Mammella), in particular: Bernard Peissel, Dario Zimbalatti, Daniela Zaffaroni, Alessandra Viel, Giuseppe Giannini Liliana Varesco, Viviana Gismondi, Maria Grazia Tibiletti, Daniela Furlan, Antonella Savarese, Aline Martayan, Stefania Tommasi, Brunella Pilato and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy. Ms. JoEllen Weaver and Dr. Betsy Bove; FPGMX: members of the Cancer Genetics group (IDIS): Marta Santamarina, Miguel Aguado and Olivia Rios; IFE - Leipzig Research Centre for Civilization Diseases (Markus Loeffler, Joachim Thiery, Matthias Nuchter, Ronny Baber); We thank all participants, clinicians, family doctors, researchers, and technicians for their contributions and commitment to the DKFZ study and the collaborating groups in Lahore, Pakistan (Noor Muhammad, Sidra Gull, Seerat Bajwa, Faiz Ali Khan, Humaira Naeemi, Saima Faisal, Asif Loya, Mohammed Aasim Yusuf) and Bogota, Colombia (Ignacio Briceno, Fabian Gil). Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study is a study from the National Cancer Genetics Network UNICANCER Genetic Group, France. We wish to pay a tribute to Olga M. Sinilnikova, who with Dominique Stoppa-Lyonnet initiated and coordinated GEMO until she sadly passed away on the 30th June 2014. The team in Lyon (Olga Sinilnikova, Melanie Leone, Laure Barjhoux, Carole Verny-Pierre, Sylvie Mazoyer, Francesca Damiola, Valerie Sornin) managed the GEMO samples until the biological resource centre was transferred to Paris in December 2015 (Noura Mebirouk, Fabienne Lesueur, Dominique Stoppa-Lyonnet). We want to thank all the GEMO collaborating groups for their contribution to this study: Coordinating Centre, Service de Genetique, Institut Curie, Paris, France: Muriel Belotti, Ophelie Bertrand, Anne-Marie Birot, Bruno Buecher, Sandrine Caputo, Anais Dupre, Emmanuelle Fourme, Marion Gauthier-Villars, Lisa Golmard, Claude Houdayer, Marine Le Mentec, Virginie Moncoutier, Antoine de Pauw, Claire Saule, Dominique Stoppa-Lyonnet, and Inserm U900, Institut Curie, Paris, France: Fabienne Lesueur, Noura Mebirouk. Contributing Centres: Unite Mixte de Genetique Constitutionnelle des Cancers Frequents, Hospices Civils de Lyon - Centre Leon Berard, Lyon, France: Nadia Boutry-Kryza, Alain Calender, Sophie Giraud, Melanie Leone. Institut Gustave Roussy, Villejuif, France: Brigitte Bressac-de-Paillerets, Olivier Caron, Marine Guillaud-Bataille. Centre Jean Perrin, Clermont-Ferrand, France: Yves-Jean Bignon, Nancy Uhrhammer. Centre Leon Berard, Lyon, France: Valerie Bonadona, Christine Lasset. Centre Francois Baclesse, Caen, France: Pascaline Berthet, Laurent Castera, Dominique Vaur. Institut Paoli Calmettes, Marseille, France: Violaine Bourdon, Catherine Nogues, Tetsuro Noguchi, Cornel Popovici, Audrey Remenieras, Hagay Sobol. CHU Arnaud-de-Villeneuve, Montpellier, France: Isabelle Coupier, Pascal Pujol. Centre Oscar Lambret, Lille, France: Claude Adenis, Aurelie Dumont, Francoise Revillion. Centre Paul Strauss, Strasbourg, France: Daniele Muller. Institut Bergonie, Bordeaux, France: Emmanuelle Barouk-Simonet, Francoise Bonnet, Virginie Bubien, Michel Longy, Nicolas Sevenet, Institut Claudius Regaud, Toulouse, France: Laurence Gladieff, Rosine Guimbaud, Viviane Feillel, Christine Toulas. CHU Grenoble, France: Helene Dreyfus, Christine Dominique Leroux, Magalie Peysselon, Rebischung. CHU Dijon, France: Amandine Baurand, Geoffrey Bertolone, Fanny Coron, Laurence Faivre, Caroline Jacquot, Sarab Lizard. CHU St-Etienne, France: Caroline Kientz, Marine Lebrun, Fabienne Prieur. Hotel Dieu Centre Hospitalier, Chambery, France: Sandra Fert Ferrer. Centre Antoine Lacassagne, Nice, France: Veronique Mari. CHU Limoges, France: Laurence Venat-Bouvet. CHU Nantes, France: Stephane Bezieau, Capucine Delnatte. CHU Bretonneau, Tours and Centre Hospitalier de Bourges France: Isabelle Mortemousque. Groupe Hospitalier Pitie-Salpetriere, Paris, France: Chrystelle Colas, Florence Coulet, Florent Soubrier, Mathilde Warcoin. CHU Vandoeuvre-les-Nancy, France: Myriam Bronner, Johanna Sokolowska. CHU Besancon, France: Marie-Agnes Collonge-Rame, Alexandre Damette. CHU Poitiers, Centre Hospitalier d'Angouleme and Centre Hospitalier de Niort, France: Paul Gesta. Centre Hospitalier de La Rochelle: Hakima Lallaoui. CHU Nimes Caremeau, France: Jean Chiesa. CHI Poissy, France: Denise Molina-Gomes. CHU Angers, France: Olivier Ingster; Ilse Coene en Brecht Crombez; Ilse Coene and Brecht Crombez; Alicia Tosar and Paula Diaque; Drs.Sofia Khan, Taru A. Muranen, Carl Blomqvist, Irja Erkkila and Virpi Palola; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, S. Verhoef, M.K. Schmidt, N.S. Russell, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collee, A.M.W. van den Ouweland, M.J. Hooning, C. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, J.T. Wijnen, R.A.E.M. Tollenaar, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, R.B. van der Luijt, C.C. van der Pol; Amsterdam Medical Center, NL: C.M. Aalfs, T.A.M. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, NL: E.B. Gomez-Garcia, M.J. Blok; University Medical Center Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Foundation for the detection of hereditary tumours, Leiden, NL: H.F. Vasen; The Netherlands Comprehensive Cancer Organization (IKNL): S. Siesling, J.Verloop; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; the ICO Hereditary Cancer Program team led by Dr. Gabriel Capella; Dr Martine Dumont for sample management and skillful assistance; Ana Peixoto, Catarina Santos and Pedro Pinto; members of the Center of Molecular Diagnosis, Oncogenetics Department and Molecular Oncology Research Center of Barretos Cancer Hospital; Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow-Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab; the investigators of the Australia New Zealand NRG Oncology group; members and participants in the Ontario Cancer Genetics Network; Leigha Senter, Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O'Conor; HVH: acknowledgments to the Cellex Foundation for providing research facilities and equipment. Dr Juliette Coignard was supported by a fellowship of INCa Institut National du Cancer N degrees 2015-181, la Ligue Nationale contre le Cancer IP/SC-15229 and Olga Sinilnikova's fellowship (2016). BCAC Funding. BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Communitys Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH Grant U19 CA148065, and Cancer UK Grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH-129344) and, the Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec and the PSRSIIRI-701 grant, and the Quebec Breast Cancer Foundation. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The Australian Breast Cancer Tissue Bank (ABCTB) was supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia and acknowledges funding from the National Breast Cancer Foundation (JS). For the BCFR-NY, BCFR-PA, BCFR-UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. The BREast Oncology GAlician Network (BREOGAN) is funded by Accion Estrategica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Accion Estrategica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo-SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Conselleria de Industria Programa Sectorial de Investigacion Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigacion, Desarrollo e Innovacion Tecnologica de la Conselleria de Industria de la Xunta de Galicia, Spain; Grant EC11-192. Fomento de la Investigacion Clinica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER-Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). CBCS is funded by the Canadian Cancer Society (grant # 313404) and the Canadian Institutes of Health Research. CCGP is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale contre le Cancer, Agence Nationale de Securite Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer and the Fondo de Investigacion Sanitario (PI11/00923 and PI12/00070). The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is currently funded through the National Institutes of Health (R01 CA77398, UM1 CA164917, and U01 CA199277). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by: Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GC-HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GESBC was supported by the Deutsche Krebshilfe e. V. [70492] and the German Cancer Research Center (DKFZ). The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki UniversityHospital Research Fund, the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017), and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for support the Bioresource collections and RFBR grants 14-04-97088, 17-29-06014 and 17-44-020498. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Marit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). G.C.T. and P.W. are supported by the NHMRC. RB was a Cancer Institute NSW Clinical Research Fellow. LMBC is supported by the 'Stichting tegen Kanker'. The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419, 110826, 110828], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC; IG2014 no.15547) to P. Radice. The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785 an NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. The Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414 and 1074383 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. The MEC was support by NIH grants CA63464, CA54281, CA098758, CA132839 and CA164973. The MISS study is supported by funding from ERC-2011-294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286 and CA177150. MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program - grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade - grant # PSR-SIIRI-701. The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC-BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, U01 CA179715), and the North Carolina University Cancer Research Fund. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956 and Breast Cancer Campaign 2010PR62, 2013PR044. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318. SEARCH is funded by Cancer Research UK [C490/A10124, C490/A16561] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005 and Z01-ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation and the Swedish Research Council (VR 2017-00644) grant for the Swedish Infrastructure for Medical Population-based Life-course Environmental Research (SIMPLER). The SZBCS and IHCC were supported by Grant PBZ_KBN_122/P05/2004 and the program of the Minister of Science and Higher Education under the name Regional Initiative of Excellence in 2019-2022 project number 002/RID/2018/19 amount of financing 12 000 000 PLN. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The UCIBCS component of this research was supported by the NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. CIMBA Funding. CIMBA: The CIMBA data management and data analysis were supported by Cancer Research - UK grants C12292/A20861, C12292/A11174. GCT and ABS are NHMRC Research Fellows. iCOGS: the European Community's Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-87521), and the Ministry of Economic Development, Innovation and Export Trade (PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Quebec, and The Quebec Breast Cancer Foundation. BCFR: UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. BIDMC: Breast Cancer Research Foundation. CNIO: Spanish Ministry of Health PI16/00440 supported by FEDER funds, the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R and the Spanish Research Network on Rare diseases (CIBERER). COH-CCGCRN: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number R25CA112486, and RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CONSIT TEAM: Funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000') to S. Manoukian. Associazione Italiana Ricerca sul Cancro (AIRC; IG2015 no.16732) to P. Peterlongo. DEMOKRITOS: European Union (European Social Fund - ESF) and Greek national funds through the Operational Program Education and Lifelong Learning of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research & Technology: SYN11_10_19 NBCA. Investing in knowledge society through the European Social Fund. DKFZ: German Cancer Research Center. EMBRACE: Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: A.K.G. was in part funded by the NCI (R01 CA214545), The University of Kansas Cancer Center Support Grant (P30 CA168524), The Kansas Institute for Precision Medicine (P20 GM130423), and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. is the Chancellors Distinguished Chair in Biomedical Sciences Professorship. A.Vega is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant numbers: INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigacion Biomedica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundacion Mutua Madrilena (call 2018). GC-HBOC: German Cancer Aid (grant no 110837, Rita K. Schmutzler) and the European Regional Development Fund and Free State of Saxony, Germany (LIFE - Leipzig Research Centre for Civilization Diseases, project numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: Ligue Nationale Contre le Cancer; the Association Le cancer du sein, parlons-en! Award, the Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program and the French National Institute of Cancer (INCa grants 2013-1-BCB-01-ICH-1 and SHS-E-SP 18-015). GEORGETOWN: the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Hereditary Cancer and Clinical Genomics Research, and Swing Fore the Cure. G-FAST: Bruce Poppe is a senior clinical investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. HCSC: Spanish Ministry of Health PI15/00059, PI16/01292, and CB-161200301 CIBERONC from ISCIII (Spain), partially supported by European Regional Development FEDER funds. HEBCS: Helsinki University Hospital Research Fund, the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON: the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014-187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HEBON thanks the registration teams of Dutch Cancer Registry (IKNL; S. Siesling, J. Verloop) and the Dutch Pathology database (PALGA; L. Overbeek) for part of the data collection. ICO: The authors would like to particularly acknowledge the support of the Asociacion Espanola Contra el Cancer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economia y Competitividad) and Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563 and CIBERONC) and the Institut Catala de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). INHERIT: Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program - grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade - grant # PSR-SIIRI-701. IOVHBOCS: Ministero della Salute and 5x1000 Istituto Oncologico Veneto grant. kConFab: The National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. MAYO: NIH grants CA116167, CA192393 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201),and a grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. Marc Tischkowitz is supported by the funded by the European Union Seventh Framework Program (2007Y2013)/European Research Council (Grant No. 310018). MSKCC: the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, the Andrew Sabin Research Fund and a Cancer Center Support Grant/Core Grant (P30 CA008748). NCI: the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50, N02-CP-21013-63 and N02-CP-65504 with Westat, Inc, Rockville, MD. NNPIO: the Russian Foundation for Basic Research (grants 17-00-00171, 18-515-45012 and 19-515-25001). NRG Oncology: U10 CA180868, NRG SDMC grant U10 CA180822, NRG Administrative Office and the NRG Tissue Bank (CA 27469), the NRG Statistical and Data Center (CA 37517) and the Intramural Research Program, NCI. OSUCCG: Ohio State University Comprehensive Cancer Center. PBCS: Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumours (ITT) grant 2014-2015-2016. SMC: the Israeli Cancer Association. SWE-BRCA: the Swedish Cancer Society. UCHICAGO: NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UPENN: Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. UPITT/MWH: Hackers for Hope Pittsburgh. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. HVH: Supported by the Carlos III National Health Institute funded by FEDER funds - a way to build Europe - PI16/11363. MT Parsons is supported by a grant from Newcastle University. Kelly-Anne Phillips is an Australian National Breast Cancer Foundation Fellow. ; Sí

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10(-20)), ER-negative BC (P=1.1 × 10(-13)), BRCA1-associated BC (P=7.7 × 10(-16)) and triple negative BC (P-diff=2 × 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10(-3)) and ABHD8 (P<2 × 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk. ; We thank all the individuals who took part in these studies and all the researchers, clin- icians, technicians and administrative staff who have enabled this work to be carried out, in particular those involved in the COGS project: Rosalind A. Eeles, Ali Amin Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Andrew Lee, and Ed Dicks, Craig Luccarini and the staff of the Centre for Genetic Epidemiology Laboratory, the staff of the CNIO genotyping unit, Daniel C. Tessier, Francois Bacot, Daniel Vincent, Sylvie LaBoissie ` re and Frederic Robidoux and the staff of the McGill University and Ge ́ nome Que ́ bec Innovation Centre, Sune F. Nielsen, Borge G. Nordestgaard, and the staff of the Copenhagen DNA laboratory, and Julie M. Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer and the staff of Mayo Clinic Genotyping Core Facility. BCAC (acknowledgements by study) (ABCFS) : Maggie Angelakos, Judi Maskiell, Gillian Dite. (ABCS) C Ellen van der Schoot, Sanquin Amsterdam. (ACP) The ACP study wishes to thank the participants in the Thai Breast Cancer study. Special Thanks also go to the Thai Ministry of Public Health (MOPH), doctors and nurses who helped with the data collection process. Finally, the study would like to thank Dr Prat Boonyawongviroj, the former Permanent Secretary of MOPH and Dr Pornthep Siriwanarungsan, the Department Director-Generalof Disease Control who have supported the study throughout. (BBCS) Eileen Williams, Elaine Ryder-Mills, Kara Sargus (BIGGS) Niall McInerney, Gabrielle Colleran, Andrew Rowan, Angela Jones. (BSUCH) Peter Bugert, Medical Faculty Mannheim (CGPS) Staff and participants of the Copenhagen General Population Study. For the excellent technical assistance: Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, Dorthe Kjeldgård Hansen (CNIO-BCS) Guillermo Pita, Charo Alonso, Daniel Herrero, Nuria A ́ lvarez, Pilar Zamora, Primitiva Menendez, the Human Genotyping-CEGEN Unit (CNIO)(CTS). The CTS Steering Committee includes Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma, Yani Lu, and Jessica Clague DeHart at the Beckman Research Institute of City of Hope, Dennis Deapen, Rich Pinder, Eunjung Lee, and Fred Schumacher at the University of Southern California, Pam Horn-Ross, Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer Prevention Institute of California, and Hoda Anton-Culver, Argyrios Ziogas, and Hannah Park at the University of California Irvine. (ESTHER) Hartwig Ziegler, Sonja Wolf, Volker Hermann. (GC-HBOC) Heide Hellebrand, Stefanie Engert and GC-HBOC (Supported by Deutsche Krebshilfe). (GENICA) The GENICA Network: Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tu ̈bingen, Germany [HB, Wing-Yee Lo, Christina Justenhoven], German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) [HB], Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany [Yon-Dschun Ko, Christian Baisch], Institute of Pathology, University of Bonn, Germany [Hans-Peter Fischer], Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany [UH], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, Germany [Thomas Bru ̈ning, Beate Pesch, Sylvia Rabstein, Anne Lotz]; and Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth] (HEBCS) Kirsimari Aaltonen, Karl von Smitten, Sofia Khan, Tuomas Heikkinen, Irja Erkkila ̈ . (HMBCS) Natalia Antonenkova, Peter Hillemanns, Hans Christiansen and Johann H. Karstens (KBCP) Eija Myo ̈ ha ̈ nen, Helena Kemila ̈ inen. (kConFab/AOCS) We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. (LAABC) We thank all the study participants and the entire data collection team, especially Annie Fung and June Yashiki. (LMBC) Gilian Peuteman, Dominiek Smeets, Thomas Van Brussel and Kathleen Corthouts. (MARIE) Petra Seibold, Judith Heinz, Nadia Obi, Alina Vrieling, Sabine Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers and Stefan Nickels. (MCCS) MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry (VCR) and the Australian Institute of Health and Welfare (AIHW), including the National Death Index. (MBCSG) Bernard Peissel and Daniela Zaffaroni and Giulietta Scuvera of the Fondazione IRCCS Istituto Nazionale dei Tumori (INT), Milan, Italy; Monica Barile and Irene Feroce of the Istituto Europeo di Oncologia (IEO), Milan, Italy; and the personnel of the Cogentech Cancer Genetic Test Laboratory. (MTLGEBCS) We would like to thank Martine Tranchant (CHU de Que ́ bec Research Center), Marie-France Valois, Annie Turgeon and Lea Heguy (McGill University Health Center, Royal Victoria Hospital; McGill Uni- versity) for DNA extraction, sample management and skilful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. (MYBRCA) Phuah Sze Yee, Peter Kang, Kang In Nee, Kavitta Sivanandan, Shivaani Mariapun, Yoon Sook-Yee, Daphne Lee, Teh Yew Ching and Nur Aishah Mohd Taib for DNA Extraction and patient recruitment. (NBHS) We thank study partcipants and research staff for their contributions and commitment to this study. (OBCS) Meeri Otsukka, Kari Mono- nen(OFBCR) Teresa Selander, Nayana Weerasooriya(ORIGO) We thank E. Krol-War- merdam, and J. Blom for patient accrual, administering questionnaires, and managing clinical information. The LUMC survival data were retrieved from the Leiden hospital- based cancer registry system (ONCDOC) with the help of Dr J. Molenaar. (PBCS) Louise Brinton, Mark Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski, Pei Chao, Michael Stagner(pKARMA) The Swedish Medical Research Counsel. (RBCS) Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Annette Heemskerk, the Erasmus MC Family Cancer Clinic. (SASBAC) The Swedish Medical Research Counsel. (SBCGS) We thank study partcipants and research staff for their contributions and commitment to this study. (SBCS) Sue Higham, Helen Cramp, Ian Brock, Malcolm W. R. Reed, Sabapathy Balasubramanian and Dan Connley. (SEARCH) The SEARCH and EPIC teams. (SGBCC) We thank the participants and research coordinator Kimberley Chua. (SKKDKFZS) We thank all study participants, clinicians, family doctors, researchers and technicians for their contributions and commitment to this study. (TNBCC) Robert Pilarski and Charles Shapiro were instrumental in the formation of the OSU Breast Cancer Tissue Bank. We thank the Human Genetics Sample Bank for processing of samples and providing OSU Columbus area control samples. (UKBGS) We thank Breakthrough Breast Cancer and the Institute of Cancer Research for support and funding of the Breakthrough Generations Study, and the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. We acknowledge NHS funding to the Royal Marsden/ ICR NIHR Biomedical Research Centre. OCAC (acknowledgements by study) : This study would not have been possible without the contributions of the following: J Dennis, P. Hall (COGS); D. C. Tessier, F. Bacot, D. Vincent, S. LaBoissie ` re and F. Robidoux and the staff of the genotyping unit, (Genome Quebec); D. C. Whiteman, P. M. Webb, A. C. Green, N. K. Hayward, P. G. Parsons, D. M. Purdie, B. M. Smithers, D. Gotley, A. Clouston, I. Brown, S. Moore. K. Harrap, T. Sadkowski, S. O'Brien, E. Minehan, D. Roffe, S. O'Keefe, S. Lipshut, G. Connor . Berry, F. Walker, T. Barnes, J. Thomas, L. Terry, M. Connard, L. Bowes, M-R. Malt, J. White, C. Mosse, N. Tait, C. Bambach, A. Biankan, R. Brancatisano, M. Coleman, M. Cox, S. Deane, G. L. Falk, J. Gallagher, M. Hollands, T. Hugh, D. Hunt, J. Jorgensen, C. Martin, M. Richardson, G. Smith, R. Smith, D. Storey, J. Avramovic, J. Croese, J. D'Arcy, S. Fairley, J. Hansen, J. Masson, L. Nathanson, B. O'Loughlin, L. Rutherford, R. Turner, M. Windsor, J. Bessell, P. Devitt, G. Jamieson, D. Watson, S. Blamey, A. Boussioutas, R. Cade, G. Crosthwaite, I. Faragher, J. Gribbin, G. Hebbard, G. Kiroff, B. Mann, R. Millar, P. O'Brien, R. Thomas, S. Wood, S. Archer, K. Faulkner, J. Hamdorf (ACS); R. Stuart-Harris, F. Kirsten, J. Rutovitz, P. Clingan, A.Glasgow, A. Proietto, S. Braye, G. Otton, J. Shannon, T. Bonaventura, J. Stewart, S. Begbie, M. Friedlander, D. Bell, S. Baron-Hay, G. Gard, D. Nevell, N. Pavlakis, S. Valmadre, B. Young, C Camaris, R. Crouch, L. Edwards, N. Hacker, D. Marsden, G. Robertson, P. Beale, J. Beith, J. Carter, C. Dalrymple, R. Houghton, P. Russell, L. Anderson, M. Links, J. Grygiel, J. Hill, A. Brand, K. Byth, R. Jaworski, P. Harnett, R. Sharma,.G Wain, D. Purdie, D. Whiteman, B. Ward, D. Papadimos, A. Crandon, M. Cummings, K. Horwood. A. Obermair, L. Perrin, D. Wyld, J. Nicklin, M. Davy, M. K. Oehler, C. Hall, T. Dodd, T. Healy, K. Pittman, D. Henderson, J. Miller, J. Pierdes, A. Achan, P. Blomfield, D. Challis, R. McIntosh, A. Parker, B. Brown, R. Rome, D. Allen, P. Grant, S. Hyde, R. Laurie, M. Robbie, D. Healy, T. Jobling, T. Manolitsas, J. McNealage, P Rogers, B. Susil, E. Sumithran, I. Simpson, I. Haviv, K. Phillips, D. Rischin, S. Fox, D. Johnson, S. Lade, P. Waring, M. Loughrey, N.O'Callaghan, B. Murray, L. Mileshkin, P. Allan; V. Billson, J. Pyman, D. Neesham, M. Quinn, A. Hamilton, C. Underhill, R. Bell, L. F Ng, R. Blum, V.Ganju, I. Hammond, C. Stewart, Y. Leung, M. Buck, N. Zeps (ACS); G. Peuteman, T. Van Brussel and D. Smeets (BEL); U. Eilber and T. Koehler (GER); L. Gacucova (HMO); P. Schu ̈rmann, F. Kramer, W. Zheng, T.-W. Park-Simon, K. Beer-Grondke and D. Schmidt (HJO); G.S. Keeney, S. Windebank, C. Hilker and J. Vollenweider (MAY); the state cancer registries of AL, AZ, AR, CA, CO, CT, DE, FL, GA, HI, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WYL (NHS); L. Paddock, M. King, U. Chandran, A. Samoila, and Y. Bensman (NJO); L. Brinton, M. Sherman, A. Hutchinson, N. Szeszenia- Dabrowska, B. Peplonska, W. Zatonski, A. Soni, P. Chao and M. Stagner (POL); ); C. Luccarini, P. Harrington the SEARCH team and ECRIC (SEA); the Scottish Gynaecological Clinical Trails group and SCOTROC1 investigators (SRO); W-H. Chow, Y-T. Gao (SWH); Information about TCGA and the investigators and institutions who constitute the TCGA research network can be found at http://cancergenome.nih.gov/ (TCGA); I. Jacobs, M. Widschwendter, E. Wozniak, N. Balogun, A. Ryan and J. Ford (UKO); Carole Pye (UKR); a full list of the investigators who contributed to the generation of the WTCCC data is available from http://www.wtccc.org.uk/ (WTCCC). CIMBA (acknowledgements by study) : (BCFR-AU) Maggie Angelakos, Judi Maskiell, Gillian Dite, Helen Tsimiklis. (BCFR-NY) We wish to thank members and participants in the New York site of the Breast Cancer Family Registry for their contributions to the study. (BCFR-ON) We wish to thank members and participants in the Ontario Familial Breast Cancer Registry for their contributions to the study. (BFBOCC-LT) We acknowledge Vilius Rudaitis, Laimonas Gris ˇ kevic ˇ ius, Ramu ̄ nas Janavic ˇ ius (if not in the authorship). BFBOCC-LV acknowledge Drs Janis Eglitis, Anna Krilova and Aivars Stengrevics. (BMBSA) We wish to thank the families who contribute to the BMBSA study. (BRICOH) We wish to thank Yuan Chun Ding and Linda Steele for their work in participant enrolment and biospecimen and data management.(CNIO) We thank Alicia Barroso, Rosario Alonso and Guillermo Pita for their assistance. (CONSIT TEAM) Alessandra Viel and Riccardo Dolcetti of the CRO Aviano National Cancer Institute, Aviano (PN), Italy; Laura Ottini of the 'Sapienza' University, Rome, Italy; Liliana Varesco of the IRCCS AOU San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; Laura Papi and Gabriele Capone of the University of Florence, Florence, Italy; Antonella Savarese and Aline Martayan of the Istituto Nazionale Tumori Regina Elena, Rome, Italy; Stefania Tommasi and Brunella Pilato of the Istituto Nazionale Tumori 'Giovanni Paolo II', Bari, Italy. (CORE) The CIMBA data management and analysis is funded through Cancer Research- UK grant C12292/A11174. ACA is a Senior Cancer Research - UK Research Fellow. (EMBRACE) RE is supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. (FCCC) We thank Ms. JoEllen Weaver and Dr Betsy Bove for their technical support. (GEMO) Genetic Modifiers of Cancer Risk in BRCA1/2 Mutation Carriers (GEMO) study: National Cancer Genetics Network ) UNICANCER Genetic Group * , France. We wish to thank all the GEMO collaborating groups for their contribution to this study. GEMO Collaborating Centres are: Coordinating Centres, Unite ́ Mixte de Ge ́ ne ́ tique Constitutionnelle des Cancers Fre ́ quents, Hospices Civils de Lyon - Centre Le ́ on Be ́ rard, and Equipe ) Ge ́ ne ́ tique du cancer du sein * , Centre de Recherche en Cance ́ rologie de Lyon: Olga Sinilnikova w , Sylvie Mazoyer, Francesca Damiola, Laure Barjhoux, Carole Verny-Pierre, Me ́ lanie Le ́ one, Nadia Boutry-Kryza, Alain Calender, Sophie Giraud; and Service de Ge ́ ne ́ tique Oncologique, Institut Curie, Paris: Dominique Stoppa-Lyonnet, Marion Gauthier-Villars, Bruno Buecher, Claude Houdayer, Etienne Rouleau, Lisa Golmard, Agne ` s Collet, Virginie Moncoutier, Ce ́ drick Lefol, Muriel Belotti, Antoine de Pauw, Camille Elan, Catherine Nogues, Emmanuelle Fourme, Anne-Marie Birot. Institut Gustave Roussy, Villejuif: Brigitte Bressac-de-Pail- lerets, Olivier Caron, Marine Guillaud-Bataille. Centre Jean Perrin, Clermont–Ferrand: Yves-Jean Bignon, Nancy Uhrhammer. Centre Le ́ on Be ́ rard, Lyon: Christine Lasset, Vale ́ rie Bonadona, Sandrine Handallou. Centre Franc ̧ ois Baclesse, Caen: Agne ` s Hardouin, Pascaline Berthet, Dominique Vaur, Laurent Castera. Institut Paoli Calmettes, Marseille: Hagay Sobol, Violaine Bourdon, Tetsuro Noguchi, Audrey Remenieras, Franc ̧ ois Eisinger. CHU Arnaud-de-Villeneuve, Montpellier: Isabelle Coupier, Pascal Pujol. Centre Oscar Lambret, Lille: Jean-Philippe Peyrat, Joe ̈ lle Fournier, Franc ̧ oise Re ́ villion, Philippe Vennin w , Claude Adenis. Centre Paul Strauss, Strasbourg: Danie ` le Muller, Jean-Pierre Fricker. Institut Bergonie ́ , Bordeaux: Emmanuelle Barouk-Simonet, Franc ̧ oise Bonnet, Virginie Bubien, Nicolas Sevenet, Michel Longy. Institut Claudius Regaud, Toulouse: Christine Toulas, Rosine Guimbaud, Laurence Gladieff, Viviane Feillel. CHU Grenoble: Dominique Leroux, He ́ le ` ne Dreyfus, Christine Rebischung, Magalie Peysselon. CHU Dijon: Fanny Coron, Laurence Faivre. CHU St-Etienne: Fabienne Prieur, Marine Lebrun, Caroline Kientz. Ho ˆ tel Dieu Centre Hospitalier, Chambe ́ ry: Sandra Fert Ferrer. Centre Antoine Lacassagne, Nice: Marc Fre ́ nay. CHU Limoges: Laurence Ve ́ nat-Bouvet. CHU Nantes: Capucine Delnatte. CHU Bretonneau, Tours: Isabelle Mortemousque. Groupe Hospitalier Pitie ́ -Salpe ́ trie ` re, Paris: Florence Coulet, Chrystelle Colas, Florent Soubrier, Mathilde Warcoin. CHU Vandoeuvre-les- Nancy: Johanna Sokolowska, Myriam Bronner. CHU Besanc ̧ on: Marie-Agne ` s Collonge- Rame, Alexandre Damette. Creighton University, Omaha, USA: Henry T. Lynch, Carrie L. Snyder. (G-FAST) We wish to thank the technical support of Ilse Coene en Brecht Crombez. (HCSC) We acknowledge Alicia Tosar for her technical assistance(HEBCS) HEBCS would like to thank Dr Kristiina Aittoma ̈ ki, Taru A. Muranen, Drs Carl Blomqvist and Kirsimari Aaltonen and RNs Irja Erkkila ̈ and Virpi Palola for their help with the HEBCS data and samples. (HEBON) The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centres: Coordinating center: Netherlands Cancer Institute, Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, S. Verhoef, M.K. Schmidt, N.S. Russell, J.L. de Lange, R. Wijnands; Erasmus Medical Center, Rotterdam, NL: J.M. Colle ́ e, A.M.W. van den Ouweland, M.J. Hooning, C. Seynaeve, C.H.M. van Deurzen, I.M. Obdeijn; Leiden University Medical Center, NL: C.J. van Asperen, J.T. Wijnen, R.A.E.M. Tollenaar, P. Devilee, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: C.M. Kets, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, R.B. van der Luijt, C.C. van der Pol; Amsterdam Medical Center, NL: C.M. Aalfs, T.A.M. van Os; VU University Medical Center, Amsterdam, NL: J.J.P. Gille, Q. Waisfisz, H.E.J. Meijers-Heijboer; University Hospital Maastricht, NL: E.B. Go ́ mez- Garcia, M.J. Blok; University Medical Center Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J. Mourits, G.H. de Bock; The Netherlands Foundation for the detection of hereditary tumours, Leiden, NL: H.F. Vasen; The Netherlands Comprehensive Cancer Organization (IKNL): S. Siesling, J.Verloop; The Dutch Pathology Registry (PALGA): L.I.H. Overbeek. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scien- tific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014- 187.WO76, the BBMRI grant NWO 184.021.007/CP46 and the Transcan grant JTC 2012 Cancer 12-054. HEBON thanks the registration teams of IKNL and PALGA for part of the data collection. (HRBCP) We wish to thank Hong Kong Sanatoriuma and Hospital for their continual support. (HUNBOCS) We wish to thank the Hungarian Breast and Ovarian Cancer Study Group members (Janos Papp, Tibor Vaszko, Aniko Bozsik, Timea Pocza, Judit Franko, Maria Balogh, Gabriella Domokos, Judit Ferenczi, Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary) and the clin- icians and patients for their contributions to this study.(HVH) We wish to thank the Oncogenetics Group (VHIO), and the High Risk and Cancer Prevention Unit of the University Hospital Vall d'Hebron.(ICO) We wish to thank the ICO Hereditary Cancer Program team led by Dr Gabriel Capella. (INHERIT) We would like to thank Dr Martine Dumont, Martine Tranchant for sample management and skilful technical assistance. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. J.S. and P.S. were part of the QC and Genotyping coordinating group of iCOGS (BCAC and CIMBA). (IPOBCS) We wish to thank Drs Ana Peixoto, Catarina Santos, Patrı ́ cia Rocha and Pedro Pinto for their skilful contribution to the study. (KCONFAB) We wish to thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics, and the Clinical Follow Up Study (which has received funding from the NHMRC, the National Breast Cancer Foundation, Cancer Australia, and the National Institute of Health (USA)) for their contributions to this resource, and the many families who contribute to kConFab. (MODSQUAD) Modifier Study of Quantitative Effects on Disease (MODSQUAD): we acknowledge ModSQuaD members Csilla Szabo (National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA); Lenka Foretova and Eva Machackova (Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Brno, Czech Republic); and Michal Zikan, Petr Pohlreich and Zdenek Kleibl (Oncogynecologic Center and Department of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University, Prague, Czech Republic). (MSKCC) Anne Lincoln, Lauren Jacobs. (NICCC) We wish to thank the NICCC National Familial Cancer Consultation Service team led by Sara Dishon, the lab team led by Dr Flavio Lejbkowicz, and the research field operations team led by Dr Mila Pinchev. (NRG Oncology) We thank the investigators of the Australia New Zealand NRG Oncology group. (OCGN) We wish to thank members and participants in the Ontario Cancer Genetics Network for their contributions to the study. (OSU CCG) Leigha Senter, Kevin Sweet, Caroline Craven, and Michelle O'Conor were instrumental in accrual of study participants, ascertainment of medical records and database management. Samples were processed by the OSU Human Genetics Sample Bank. (SEABASS) We would like to thank Yip Cheng Har, Nur Aishah Mohd Taib, Phuah Sze Yee, Norhashimah Hassan and all the research nurses, research assistants and doctors involved in the MyBrCa Study for assistance in patient recruitment, data collection and sample preparation. In addition, we thank Philip Iau, Sng Jen-Hwei and Sharifah Nor Akmal for contributing samples from the Singapore Breast Cancer Study nd the HUKM-HKL Study respectively. The Malaysian Breast Cancer Genetic Study is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HIR/MOHE/06) and charitable funding from Cancer Research Initiatives Foundation. (SMC) SMC team wishes to acknowledge the assistance of the Meirav Comprehensice breast cancer center team at the Sheba Medical Center for assistance in this study. (SWE-BRCA) Swedish scientists participating as SWE-BRCA collaborators are: from Lund University and University Hospital: Åke Borg, Håkan Olsson, Helena Jernstro ̈ m, Karin Henriksson, Katja Harbst, Maria Soller, Ulf Kristoffersson; from Gothenburg Sahlgrenska University Hospital: Anna O ̈ fverholm, Margareta Nordling, Per Karlsson, Zakaria Einbeigi; from Stockholm and Karolinska University Hospital: Anna von Wachenfeldt, Annelie Liljegren, Annika Lindblom, Brita Arver, Gisela Barbany Bustinza, Johanna Rantala; from Umeå University Hospital: Beatrice Melin, Christina Edwinsdotter Ardnor, Monica Emanuelsson; from Uppsala University: Hans Ehrencrona, Maritta Hellstro ̈ m Pigg, Richard Rosenquist; from Linko ̈ ping University Hospital: Marie Stenmark-Askmalm, Sigrun Lied- gren(UCHICAGO) We wish to thank Cecilia Zvocec, Qun Niu, physicians, genetic counsellors, research nurses and staff of the Cancer Risk Clinic for their contributions to this resource, and the many families who contribute to our programme. (UCLA) We thank Joyce Seldon MSGC and Lorna Kwan, MPH for assembling the data for this study. (UCSF) We would like to thank Dr Robert Nussbaum and the following genetic coun- sellors for participant recruitment: Beth Crawford, Kate Loranger, Julie Mak, Nicola Stewart, Robin Lee, Amie Blanco and Peggy Conrad. And thanks to Ms. Salina Chan for her data management. (UKFOCR) We thank Carole Pye, Patricia Harrington and Eva Wozniak for their contributions towards the UKFOCR. (VFCTG) Geoffrey Lindeman, Marion Harris, Martin Delatycki of the Victorian Familial Cancer Trials Group. We thank Sarah Sawyer and Rebecca Driessen for assembling this data and Ella Thompson for performing all DNA amplification. Grant Support : The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175—HEALTH-F2-2009- 223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community ́ s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The CIMBA data management and analytical work is funded by Cancer Research UK (C12292/A11174, C12292/A20861). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n ° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME-ON Post-GWAS Initiative (U19-CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based on data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute. Personal support: K.L. is supported by a K99/R00 grant from the National Cancer Institute (Grant number 1K99CA184415-01). This project was supported in part by a Program Project Development Grant from the Ovarian Cancer Research Fund (S.A.G and A.M). The in vitro aspects of this project were performed within the Norris Cancer Centre at USC, which is supported in part by award number P30CA014089 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. D.F.E. is a Principal Research Fellow of Cancer Research UK. A.C.A. is a Cancer Research—UK Senior Cancer Research Fellow. G.C.-T. and P.M.W. are supported by the National Health and Medical Research Council. (WCP) B.Y.K is funded by the American Cancer Society Early Detection Professorship (SIOP- 06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. L.E.K. is supported by a Canadian Institutes of Health Research Investigator award (MSH-87734). S.P.K. is supported by a Gates Cambridge Scholarship. J.S. is Chairholder of the Canada Research Chair in Oncogenetics. RB was a Cancer Institute NSW Clinical Research Fellow. M.C.S. is a NHMRC Senior Research Fellow. A.K.G. was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. J.L.H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. S.L.E. and J.D.F. are supported by Fellowships from the National Breast Cancer Foundation (NBCF) Australia and NHMRC project grant (1058415). Funding : BCAC: The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. The ABCS study was supported by the Dutch Cancer Society [grants NKI 2007-3839; 2009 4363]. The ACP study is funded by the Breast Cancer Research Trust, UK. The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN).ES is supported by NIHR Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. IT is supported by the Oxford Biomedical Research Centre.The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Herlev HospitalThe CNIO-BCS was supported by the Instituto de Salud Carlos III, the Red Tema ́ tica de Investigacio ́ n Cooperativa en Ca ́ ncer and grants from the Asociacio ́ n Espan ̃ ola Contra el Ca ́ ncer and the Fondo de Investigacio ́ n Sanitario (PI11/00923 and PI12/00070). The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97-10500) and is cur- rently funded through the National Institutes of Health (R01 CA77398). Collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. HAC receives support from the Lon V Smith Foundation (LVS39420). The ESTHER study was supported by a grant from the Baden Wu ̈rttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). The GC-HBOC was supported by Deutsche Krebshilfe (107 352). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society, The Nordic Cancer Union and the Sigrid Juselius Foundation. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and by the strategic funding of the University of Eastern Finland. kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command [DAMD17-01-1-0729], Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, 199600). LAABC is supported by grants (1RB-0287, 3PB-0102, 5PB-0018, 10PB-0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP), which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. LMBC is supported by the 'Stichting tegen Kanker' (232-2008 and 196-2010). Diether Lambrechts is supported by the FWO and the KULPFV/10/016-SymBioSysII.The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I, 106332, 108253, 108419], the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. (MBCSG) is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000'). The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program – grant # CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI-701.MYBRCA is funded by research grants from the Malaysian Ministry of Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation (CARIF). Additional controls were recruited by the Singapore Eye Research Institute, which was supported by a grant from the Biomedical Research Council (BMRC08/1/35/19/550), Singapore and the National medical Research Council, Singa- pore (NMRC/CG/SERI/2010). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant number 250083, 122715 and Center of Excellence grant number 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation and the special Governmental EVO funds for Oulu University Hospital-based research activities. The Ontario Familial Breast Cancer Registry (OFBCR) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The pKARMA study was supported by Ma ̈ rit and Hans Rausings Initiative Against Breast CancerThe RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study was sup- ported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The scientific development and funding of this project were, in part, supported by the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network U19 CA148065.The SBCS was supported by Yorkshire Cancer Research S295, S299, S305PA and Sheffield Experimental Cancer Medicine Centre.SEARCH is funded by a programme grant from Cancer Research UK [C490/A10124] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge.SGBCC is funded by the NUS start-up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort Studies-Multi-ethnic cohort (SCCS-MEC), which was funded by the Biomedical Research Council, grant number: 05/ 1/21/19/425.SKKDKFZS is supported by the DKFZ. The TNBCC was supported by: a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation, the Hellenic Cooperative Oncology Group research grant (HR R_BG/04) and the Greek General Secretary for Research and Technology (GSRT) Program, Research Excellence II, the European Union (European Social Fund – ESF), and Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF) - ARISTEIA. The UKBGS is funded by Breakthrough Breast Cancer and the Institute of Cancer Research (ICR), London. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. Funding : OCAC : Funding of the constituent studies was provided by the American Cancer Society (CRTG-00-196-01-CCE); the California Cancer Research Program (00-01389 V-20170, N01-CN25403, 2II0200); the Canadian Institutes for Health Research (MOP-86727); Cancer Council Victoria; Cancer Council Queensland; Cancer Council New South Wales; Cancer Council South Australia; Cancer Council Tasmania; Cancer Foundation of Western Australia; the Cancer Institute of New Jersey; Cancer Research UK (C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689); the Celma Mastry Ovarian Cancer Foundation; the Danish Cancer Society (94-222-52); the ELAN Program of the University of Erlangen-Nuremberg; the Eve Appeal; the Helsinki University Central Hospital Research Fund; Helse Vest; Imperial Experimental Cancer Research Centre (C1312/A15589); the Norwegian Cancer Society; the Norwegian Research Council; the Ovarian Cancer Research Fund; Nationaal Kankerplan of Belgium; Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health Labour and Welfare of Japan; the L and S Milken Foun- dation; the Polish Ministry of Science and Higher Education (4 PO5C 028 14, 2 PO5A 068 27); Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation; the Roswell Park Cancer Institute Alliance Foundation; the US National Cancer Institute (K07-CA095666, K07-CA143047, K22-CA138563, N01-CN55424, N01-PC067010, N01-PC035137, P01-CA017054, P01-CA087696, P30-CA15083, P50-CA105009, P50- CA136393, R01-CA014089, R01-CA016056, R01-CA017054, R01-CA049449, R01-CA050385, R01-CA054419, R01- CA058598, R01-CA058860, R01-CA061107, R01-CA061132, R01-CA063682, R01-CA064277, R01-CA067262, R01- CA071766, R01-CA074850, R01-CA076016, R01-CA080742, R01-CA080978, R01-CA083918, R01-CA087538, R01- CA092044, R01-095023, R01-CA106414, R01-CA122443, R01-CA112523, R01-CA114343, R01-CA126841, R01- CA136924, R01-CA149429, R03-CA113148, R03-CA115195, R37-CA070867, R37-CA70867, U01-CA069417, U01- CA071966, R01-CA063678 and Intramural research funds); the US Army Medical Research and Material Command (DAMD17-98-1- 8659, DAMD17-01-1-0729, DAMD17-02-1-0666, DAMD17-02-1- 0669, W81XWH-10-1-0280); the National Health and Medical Research Council of Australia (199600 and 400281); the German Federal Ministry of Education and Research of Germany Programme of Clinical Biomedical Research (01 GB 9401); the state of Baden-Wu ̈rttemberg through Medical Faculty of the University of Ulm (P.685); the Minnesota Ovarian Cancer Alliance; the Mayo Foundation; the Fred C. and Katherine B. Andersen Foundation; the Lon V. Smith Foundation (LVS-39420); the Oak Foundation; the OHSU Foundation; the Mermaid I project; the Rudolf-Bartling Foundation; the UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge, Imperial College London, University College Hospital 'Womens Health Theme' and the Royal Marsden Hospital; WorkSafeBC. Funding : CIMBA (BCFR—all) : This work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centres in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. (BFBOCC-LT) BFBOCC is partly supported by: Lithuania (BFBOCC-LT): Research Council of Lithuania grant LIG-07/2012; (BIDMC) BIDMC is supported by the Breast Cancer Research Foundation. (BMBSA) BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg. (BRICOH) SLN was partially supported by the Morris and Horowitz Familes Endowed Professorship. (CBCS) This work was supported by the NEYE Foundation. (CNIO) This work was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilen ̃ a Foundation (FMMA) and SAF2010-20493 (COH-CCGCRN) City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. (CONSIT TEAM) Funds from Italian citizens who allocated the 5x1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects '5x1000') to Siranoush Manoukian. (CORE) The CIMBA data management and data analysis were supported by Cancer Research – UK grants C12292/A11174 and C1287/A10118.SH is supported by an NHMRC Program Grant to GCT. ACA is a Cancer Research -UK Senior Cancer Research Fellow. (DEMOKRITOS) This research has been co-financed by the European Union (European Social Fund – ESF) and Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Frame- work (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA. Investing in knowledge society through the European Social Fund.(DKFZ) The DKFZ study was supported by the DKFZ. (EMBRACE) EMBRACE is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. (FCCC) The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. (GC-HBOC) The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant no 109076, Rita K. Schmutzler) and by the Center for Molecular Medicine Cologne (CMMC). (GEMO) The study was supported by the Ligue Nationale Contre le Cancer; the Association 'Le cancer du sein, parlons-en!' Award; the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program and the French National Institute of Cancer (INCa). (GEORGETOWN) CI received support from the Non-Therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI grant P30-CA051008), the Fisher Center for Familial Cancer Research, and Swing Fore the Cure. (G-FAST) Kim De Leeneer is supported by GOA grant BOF10/ GOA/019 (Ghent University) and spearhead financing of Ghent University Hospital. (HCSC) HCSC supported by a grant RD12/0036/0006 and 12/00539 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. (HEBCS) The HEBCS was financially supported by the Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. (HEBON) The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the Netherlands Organization of Scientific Research grant NWO 91109024, the Pink Ribbon grant 110005 and the BBMRI grant NWO 184.021.007/CP46. HEBON thanks the registration teams of the Comprehensive Cancer Centre Netherlands and Comprehensive Centre South (together the Netherlands Cancer Registry) and PALGA (Dutch Pathology Registry) for part of the data collection. (HRBCP) HRBCP is supported by The Hong Kong Hereditary Breast Cancer Family Registry and the Dr Ellen Li Charitable Foundation, Hong Kong (HUNBOCS) Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research Grants KTIA-OTKA CK-80745, OTKA K-112228 and the Norwegian EEA Financial Mechanism Hu0115/NA/2008-3/OP-9. (ICO) Contract grant sponsor: Asociacio ́ n Espan ̃ ola Contra el Ca ́ ncer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract grant numbers: ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/ 00748, PI13/00285, PIE13/00022, 2009SGR290 and 2014SGR364. (IHCC) The IHCC was supported by Grant PBZ_KBN_122/P05/2004(ILUH) The ILUH group was supported by the Icelandic Association 'Walking for Breast Cancer Research' and by the Landspitali University Hospital Research Fund. (INHERIT) This work was supported by the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program, the Canadian Breast Cancer Research Alliance-grant #019511 and the Ministry of Economic Development, Innovation and Export Trade – grant # PSR-SIIRI- 701. (IOVHBOCS) IOVHBOCS is supported by Ministero della Salute and '5 1,000' Istituto Oncologico Veneto grant. (IPOBCS) This study was in part supported by Liga Portuguesa Contra o Cancro.(KCONFAB) kConFab is supported by a grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia; (KOHBRA) KOHBRA is supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs,Republic of Korea (1020350). (MAYO) MAYO is supported by NIH grants CA116167, CA128978 and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defence Ovarian Cancer Idea award (W81XWH-10-1-0341), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation. (MCGILL) Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade (MODSQUAD) MODSQUAD was supported by MH CZ - DRO (MMCI, 00209805) and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague project UNCE204024 (MZ). (MSKCC) MSKCC is supported by grants from the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, and the Andrew Sabin Research Fund. (NAROD) 1R01 CA149429- 01. (NCI) The research of Drs MH Greene, JT Loud and PL Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by support services contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc, Rockville, MD. (NICCC) NICCC is supported by Clalit Health Services in Israel. Some of it's activities are supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. (NNPIO) This work has been supported by the Russian Federation for Basic Research (grants 13-04-92613, 14-04-93959 and 15-04-01744). (NRG Oncology) This study was supported by National Cancer Institute grants to the NRG Oncology Administrative Office and Tissue Bank (CA 27469), the NRG Oncology Statistical and Data Center (CA 37517), and NRG Oncology's Cancer Prevention and Control Committee (CA 101165). (OSU CCG) OSUCCG is supported by the Ohio State University Comprehensive Cancer Center. (PBCS) This work was supported by the ITT (Istituto Toscano Tumori) grants 2011-2013. (SEABASS) Ministry of Science, Technol- ogy and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation. (SMC) This project was partially funded through a grant by the Isreal cancer association and the funding for the Israeli Inherited breast cancer consortium (SWE-BRCA) SWE-BRCA collaborators are supported by the Swedish Cancer Society. (UCHICAGO) UCHICAGO is supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032 and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance and the Breast Cancer research Foundation. OIO is an ACS Clinical Research Professor.(UCLA) Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. (UCSF) UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. (UKFOCR) UKFOCR was supported by a project grant from CRUK to Paul Pharoah. (UPENN) National Institutes of Health (NIH) (R01-CA102776 and R01- CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA. (UPITT/MWH) Frieda G. and Saul F. Shapira BRCA-Associated Cancer Research Program;Hackers for Hope Pittsburgh. (VFCTG) Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation unding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n ° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/ A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund and grants R01-CA122443 and P50-CA136393. ; Sí

Source: doi:10.1016/S0140-6736(16)31678-6 ; Background: Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes aff ecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods: We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identifi cation and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool fi rst developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. Findings: We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4–19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30–2·50 billion). Eight causes of chronic disease and injury each aff ected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-defi ciency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that aff ected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35–2·37 billion) individuals aff ected. The second and third leading impairments by number of individuals aff ected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20–30% of total disability, largely attributable to nutritional defi ciencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-defi ciency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo. Interpretation: Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profi le driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available.

Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015. Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores. Findings We generated 9·3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17·2 billion, 95% uncertainty interval [UI] 15·4–19·2 billion) and diarrhoeal diseases (2·39 billion, 2·30–2·50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2·36 billion (2·35–2·37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20–30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo. Interpretation Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. ; Funding Bill & Melinda Gates Foundation. ; Open Access funded by Bill & Melinda Gates FoundationUnder a Creative Commons license Attribution 4.0 International (CC BY 4.0)

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape. ; Funding: Funding for this study was provided by the Aarne Koskelo Foundation; the Aase and Ejner Danielsens Foundation; the Academy of Finland (40758, 41071, 77299, 102318, 104781, 117787, 117844, 118590, 120315, 121584, 123885, 124243, 124282, 126925, 129269, 129293, 129378, 130326, 134309, 134791, 136895, 139635, 211497, 263836, 263924, 1114194, 24300796); the Agency for Health Care Policy Research (HS06516); the Agency for Science, Technology and Research of Singapore (A*STAR); the Ahokas Foundation; the ALF/LUA research grant in Gothenburg; the ALK-Abello A/S (Horsholm, Denmark), Timber Merchant Vilhelm Bangs Foundation, MEKOS Laboratories Denmark; the Althingi (the Icelandic Parliament); the American Heart Association (AHA; 13POST16500011); the ANR ("Agence Nationale de la 359 Recherche"); the Ark (NHMRC Enabling Facility); the Arthritis Research UK (19542, 18030); the AstraZeneca; the Augustinus Foundation; the Australian National Health and Medical Research Council (NHMRC; 241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672, 613601 and 1011506); the Australian Research Council (ARC; DP0770096 and DP1093502); the Becket Foundation; the bi-national BMBF/ANR funded project CARDomics (01KU0908A); the Biobanking and Biomolecular Resources Research Infrastructure (BBMRINL; 184.021.007, CP 32); the Biocentrum Helsinki; the Boehringer Ingelheim Foundation; the British Heart Foundation (RG/10/12/28456, SP/04/ 002); the Canadian Institutes for Health Reseaerch (FRCN-CCT-83028); the Cancer Research UK (C490/A10124, C490/A10119); the Center for Medical Systems Biology (CMSB; NWO Genomics); the Centers for Disease Control and Prevention and Association of Schools of Public Health (1734, S043, S3486); the Centre of Excellence Baden-Wurttemberg Metabolic Disorders; the Chief Scientist Office of the Scottish Government; the Clinical Research Facility at Guys & St Thomas NHS Foundation Trust; the Contrat de Projets Etat-Region (CPER); the Croatian Science Council (Grant no. 8875); the CVON (GENIUS); the Danish Agency for Science, Technology and Innovation; the Danish Centre for Health Technology Assessment, Novo Nordisk Inc.; the Danish Council for Independent Research (DFF 1333-00124); the Danish Diabetes Association; Danish Heart Foundation; the Danish Medical Research Council; the Danish Ministry of Internal Affairs and Health; the Danish National Research Foundation; the Danish Pharmaceutical Association; Danish Pharmacists Fund; the Danish Research Council; the Deutsche Forschungsgemeinschaft; the Diabetes Hilfs-und Forschungsfonds Deutschland (DHFD); the Dr. Robert Pfleger-Stiftung; the Dresden University of Technology Funding Grant, Med Drive; the Dutch Brain Foundation; the Dutch Diabetes Research Foundation; the Dutch Economic Structure Enhancing Fund (FES); the Dutch Kidney Foundation; the Dutch Ministry for Health, Welfare and Sports; the Dutch Ministry of Economic Affairs; the Dutch Ministry of Education, Culture and Science; the Egmont Foundation; the Else Kraner-Fresenius Stiftung (2012_A147, P48/08//A11/08); the Emil Aaltonen Foundation; the Erasmus Medical Center and Erasmus University, Rotterdam; the Estonian Ministry of Science and Education (SF0180142s08); the European Commission (223004, 2004310, DGXII, FP6-EUROSPAN, FP6-EXGENESIS, FP6-LSHG-CT2006-018947, FP6-LSHG-CT-2006-01947, FP6-LSHM- CT-2004-503485, FP6-LSHM-CT-2006037593, FP6-LSHM-CT-2007-037273, FP7-201379, FP7-201668, FP7-279143, FP7-305739, FP7313010, FP7-ENGAGE-HEALTH-F4-2007-201413, FP7-EurHEALTHAgeing-277849, FP7-HEALTH-F42007-201550, HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-F2-2008-201865-GEFOS, HEALTH-F7305507 HOMAGE, LSHM-CT-2006-037593, QLG1CT-2001-01252, QLG1-CT-2002-00896, QLG2-CT2002-01254); the European Regional Development Fund (ERDF) and the Wissenschaftsoffensive TMO; the European Regional Development Fund to the Centre of Excellence in Genomics (EXCEGEN; 3.2.0304.11-0312); the European Research Council (ERC; 2011-StG-280559-SEPI, 2011-294713-EPLORE, 230374); the European Science Foundation (ESF; EU/QLRT-2001-01254); the EuroSTRESS project FP-006; the Finlands Slottery Machine Association; the Finnish Centre for Pensions (ETK); the Finnish Cultural Foundation; the Finnish Diabetes Association; the Finnish Diabetes Research Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Foundation for Pediatric Research; the Finnish Funding Agency for Technology and Innovation (40058/07); the Finnish Medical Society; the Finnish Ministry of Education and Culture (627; 2004-2011); the Finnish Ministry of Health and Social Affairs (5254); the Finnish National Public Health Institute (current National Institute for Health and Welfare); the Finnish Special Governmental Subsidy for Health Sciences; the Finska Lakaresallskapet, Signe and Ane Gyllenberg Foundation; the Flemish League against Cancer, ITEA2 (project Care4Me); the Folkhalsan Research Foundation; the Fonds voor Wetenschappelijk Onderzoek (FWO) Vlaanderen; the Foundation for Life and Health in Finland; the Foundation for Strategic Research (SSF) and the Stockholm County Council (560283); the G. Ph. Verhagen Foundation; the Gene-diet Interactions in Obesity' project (GENDINOB); the Genetic Association Information Network (GAIN); the GENEVA Coordinating Center (U01 HG 004446); the GenomEUtwin (EU/QLRT2001-01254; QLG2-CT-2002-01254); the German Bundesministerium fuer Forschung und Technology (01 AK 803 A-H, 01 IG 07015 G); the German Diabetes Association; the German Ministry of Cultural Affairs; the German Federal Ministry of Education and Research (BMBF; 03IS2061A, 03ZIK012, 01ZZ9603, 01ZZ0103, 01ZZ0403); the German National Genome Research Network (NGFN-2 and NGFN-plus); the German Research Council (SFB1052 "Obesity mechanisms"); the Great Wine Estates of the Margaret River region of Western Australia; the Greek General Secretary of Research and Technology research grant (PENED 2003); the Gyllenberg Foundation; the Health Care Centers in Vasa, Narpes and Korsholm; the Health Fund of the Danish Health Insurance Societies; the Helmholtz Zentrum Munchen-German Research Center for Environmental Health; the Helsinki University Central Hospital special government funds (EVO #TYH7215, #TKK2012005, #TYH2012209); the Hjartavernd (the Icelandic Heart Association); the Ib Henriksen Foundation; the Illinois Department of Public Health, and the Translational Genomics Research Institute; the INTERREG IV Oberrhein Program (Project A28); the Interuniversity Cardiology Institute of the Netherlands (ICIN; 09.001); the Italian Ministry of Health "targeted project" (ICS110.1/RF97.71); the Italian National Centre of Research InterOmics PB05_ SP3; the John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health; the Johns Hopkins University Center for Inherited Disease Research (CIDR); the Joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania; the Juho Vainio Foundation; the Juselius Foundation (Helsinki, Finland); the Juvenile Diabetes Research Foundation International (JDRF); the KfH Stiftung Praventivmedizin e. V.; the Knut and Alice Wallenberg Foundation; the Kuopio University Hospital; the Leenaards Foundation; the Leiden University Medical Center; the Liv och Halsa; the Local Government Pensions Institution (KEVA); the Lokaal Gezondheids Overleg (LOGO) Leuven and Hageland; the LudwigMaximilians- Universitat, as part of LMUinnovativ; the Lundberg Foundation; the March of Dimes Birth Defects Foundation; the Medical Research Council (G0601966; G0700931; G0000934; G0500539; G0600705; G1002319; G0701863; PrevMetSyn/SALVE; MC_ U106179471; MC_ UU_ 12019/1); the MRC centre for Causal Analyses in Translational Epidemiology (MRC CAiTE); the MRC Centre for Obesity and Related Metabolic Diseases; the MRC Human Genetics Unit; the Medical Research Council of Canada; the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488); the Ministry of the Flemish Community, Brussels, Belgium (G. 0881.13 and G. 0880. 13); the MIUR-CNR Italian Flagship Project; the Montreal Heart Institute Foundation; the Munich Center of Health Sciences (MC Health); the Municipal Health Care Center and Hospital in Jakobstad; the Narpes Health Care Foundation; the National Alliance for Research on Schizophrenia and Depression (NARSAD); the National Cancer Institute (CA047988); the National Center for Advancing Translational Sciences (UL1TR000124); the National Center for Research Resources (U54RR020278); the National Heart, Lung and Blood Institute (NHLBI, 1RL1MH083268-01, 5R01HL087679-02, HHSN268200800007C, HHSN268201200036C, HL043851, HL080467, HL087647, HL36310, HL45670, N01HC25195, N01HC55015, N01HC55016, N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N02HL64278, R01HL086694, R01HL087641, R01HL087652, R01HL087676, R01HL59367, R01HL103612, R01HL105756, R01HL120393, U01HL080295); the National Human Genome Research Institute (NHGRI, U01HG004402); the National Institute for Health and Welfare (THL); the National Institute for Health Research (NIHR, RP-PG-0407-10371); the National Institute of Allergy and Infectious Diseases (NIAID); the National Institute of Child Health and Human Development (NICHD); the National Institute of Diabetes and Digestive and Kidney Disease (NIDDKDRC, 1R01DK8925601, DK063491, R01DK089256, P30 DK072488); the National Institute of Food and Agriculture (2007-35205-17883); the National Institute of Neurological Disorders and Stroke (NINDS); the National Institute on Aging (NIA; 263-MA-410953, 263-MD-821336, 263-MD-9164, AG023629, AG13196, NO1AG12109, P30AG10161, R01AG15819, R01AG17917, R01AG023629, R01AG30146); the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5-P60-AR30701, 5-P60-AR49465-03); the National Institutes of Health (NIH; 1R01DK8925601, 1RC2MH089951, 1RC2MH089995, 1Z01HG000024, 2T32 HL 00705536, 5R01DK075681, 5R01MH63706: 02, AA014041, AA07535, AA10248, AA13320, AA13321, AA13326, AG028555, AG08724, AG04563, AG10175, AG08861, DA12854, DK046200, DK091718, F32AR059469, HG002651, HHSN268200625226C, HHSN268200782096C, HL084729, MH081802, N01AG12100, N01HG65403, R01AG011101, R01AG030146, R01D0042157-01A, R01DK062370, R01DK072193, R01DK093757, R01DK075787, R01DK075787, R01HL71981, R01MH59565, R01MH59566, R01MH59571, R01MH59586, R01MH59587, R01MH59588, R01MH60870, R01MH60879, R01MH61675, R01MH67257, R01MH81800, R01NS45012, U01066134, U01CA098233, U01DK062418, U01GM074518, U01HG004423, U01HG004436, U01HG004438, U01HL072515-06, U01HL105198, U01HL84756, U01MH79469, U01MH79470, U01NS069208-01, UL1RR025005); the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust; the NIHR Cambridge Biomedical research Centre; the Netherlands Heart Foundation (2001 D 032); the Netherlands Organisation for Scientific Research (NWO; Geestkracht program grant 10-000-1002; 050-060-810; 100-001-004; 175.010.2003.005; 175.010.2005.011; 175.010.2007. 006; 261-98-710; 40-0056-98-9032; 400-05-717; 452-04-314; 452-06-004; 480-01-006; 480-04-004; 480-05-003; 480-07-001; 481-08-013; 60-60600-97-118; 904-61-090; 904-61-193; 911-03012; 985-10-002; Addiction-31160008; GB-MW 94038- 011; SPI 56-464-14192); the Netherlands Organization for the Health Research and Development (ZonMw; 91111025); the Nordic Center of Excellence in Disease Genetics; the Nordic Centre of Excellence on Systems biology in controlled dietary interventions and cohort studies, SYSDIET (070014); the Northern Netherlands Collaboration of Provinces (SNN); the Novo Nordisk Foundation; the Office of Research and Development, Medical Research Service, and the Baltimore Geriatrics Research, Education, and Clinical Center of the Department of Veterans Affairs; the Ollqvist Foundation; the Paavo Nurmi Foundation; the Pahlssons Foundation; the Paivikki and Sakari Sohlberg Foundation; the Perklen Foundation; the Republic of Croatia Ministry of Science, Education and Sports research (108-1080315-0302); the Research Centre for Prevention and Health, the Capital Region of Denmark; the Research Foundation of Copenhagen County; the Research Institute for Diseases in the Elderly (014-93-015; RIDE2); the Reynold's Foundation; the Rotterdam Oncologic Thoracic Study Group, Erasmus Trust Fund, Foundation against Cancer; the Royal Swedish Academy of Science; the Russian Foundation for Basic Research (NWO-RFBR 047.017.043); the Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06); the Samfundet Folkhalsan; the Sigrid Juselius Foundation; the Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds (9M048, 9N035); the Social Ministry of the Federal State of Mecklenburg-West Pomerania; the Societe Francophone du 358 Diabste (SFD); the South Tyrolean Sparkasse Foundation; the Stichting Nationale Computerfaciliteiten (National Computing Facilities Foundation, NCF); the Strategic Cardiovascular Programme of Karolinska Institutet and the Stockholm County Council (560183); the Susan G. Komen Breast Cancer Foundation; the Swedish Cancer Society; the Swedish Cultural Foundation in Finland; the Swedish Diabetes Association; the Swedish Diabetes Foundation (grant no. 2013-024); the Swedish Foundation for Strategic Research (SSF; ICA08-0047); the Swedish HeartLung Foundation (20120197); the Swedish Medical Research Council (K2007-66X-20270-01-3, 20121397); the Swedish Ministry for Higher Education; the Swedish Research Council (8691, M-2005-1112, 2009-2298); the Swedish Society for Medical Research; the Swiss National Science Foundation (31003A-143914, 3200B0105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, 33CS30148401); SystemsX. ch (51RTP0_151019); the Tampere Tuberculosis Foundation; the TEKES (70103/06, 40058/07); the The Paul Michael Donovan Charitable Foundation; the Torsten and Ragnar Sderberg Foundation; the Umea Medical Research Foundation; the United Kingdom NIHR Cambridge Biomedical Research Centre; the Universities and Research of the Autonomous Province of Bolzano, South Tyrol; the University Hospital of Regensburg (ReForM A, ReForM C); the University Hospital Oulu, Biocenter, University of Oulu, Finland (75617); the University Medical Center Groningen; the University of Groningen; the University of Maryland General Clinical Research Center (M01RR16500, AG000219); the University of Tartu (SP1GVARENG); the University of Tromso, Norwegian Research Council (185764); the Vasterbottens Intervention Programme; the Velux Foundation; the VU University Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the Wellcome Trust (064890, 068545/Z/02, 076113/B/04/Z, 077016/Z/05/Z, 079895, 084723/Z/08/Z, 086596/Z/ 08/Z, 088869/B/09/Z, 089062, 090532, 098017, 098051, 098381); the Western Australian DNA Bank (NHMRC Enabling Facility); the Yrjo Jahnsson Foundation (56358); and the Zorg Onderzoek Nederland-Medische Wetenschappen, KWF Kankerbestrijding, Stichting Centraal Fonds Reserves van voormalig Vrijwillige Ziekenfondsverzekeringen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. More details of acknowledgements can be found in S2 Text.

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Informationen zum Inhalt können den Studiennummern ZA5179 CSES Module 1 Full Release, ZA5180 CSES Module 2 Full Release, und ZA5181 CSES Module 3 Full Release entnommen werden.