Protecting and promoting recovery of species at risk of extinction is a critical component of biodiversity conservation. In Canada, the Committee on the Status of Endangered Wildlife in Canada (COSEWIC) determines whether species are at risk of extinction or extirpation, and has conducted these assessments since 1977. We examined trends in COSEWIC assessments to identify whether at-risk species that have been assessed more than once tended to improve, remain constant, or deteriorate in status, as a way of assessing the effectiveness of biodiversity conservation in Canada. Of 369 species that met our criteria for examination, 115 deteriorated, 202 remained unchanged, and 52 improved in status. Only 20 species (5.4%) improved to the point where they were 'not at risk', and five of those were due to increased sampling efforts rather than an increase in population size. Species outcomes were also dependent on the severity of their initial assessment; for example, 47% of species that were initially listed as special concern deteriorated between assessments. After receiving an at-risk assessment by COSEWIC, a species is considered for listing under the federal Species at Risk Act (SARA), which is the primary national tool that mandates protection for at-risk species. We examined whether SARA-listing was associated with improved COSEWIC assessment outcomes relative to unlisted species. Of 305 species that had multiple assessments and were SARAlisted, 221 were listed at a level that required identification and protection of critical habitat; however, critical habitat was fully identified for only 56 of these species. We suggest that the Canadian government should formally identify and protect critical habitat, as is required by existing legislation. In addition, our finding that at-risk species in Canada rarely recover leads us to recommend that every effort be made to actively prevent species from becoming at-risk in the first place.
In: Levin , A , Tonelli , M , Bonventre , J , Coresh , J , Donner , J-A , Fogo , A B , Fox , C S , Gansevoort , R T , Heerspink , H J L , Jardine , M , Kasiske , B , Köttgen , A , Kretzler , M , Levey , A S , Luyckx , V A , Mehta , R , Moe , O , Obrador , G , Pannu , N , Parikh , C R , Perkovic , V , Pollock , C , Stenvinkel , P , Tuttle , K R , Wheeler , D C , Eckardt , K-U & ISN Global Kidney Health Summit participants 2017 , ' Global kidney health 2017 and beyond : a roadmap for closing gaps in care, research, and policy ' , The Lancet , vol. 390 , no. 10105 , pp. 1888-1917 . https://doi.org/10.1016/S0140-6736(17)30788-2 ; ISSN:0140-6736
The global nephrology community recognises the need for a cohesive plan to address the problem of chronic kidney disease (CKD). In July, 2016, the International Society of Nephrology hosted a CKD summit of more than 85 people with diverse expertise and professional backgrounds from around the globe. The purpose was to identify and prioritise key activities for the next 5-10 years in the domains of clinical care, research, and advocacy and to create an action plan and performance framework based on ten themes: strengthen CKD surveillance; tackle major risk factors for CKD; reduce acute kidney injury-a special risk factor for CKD; enhance understanding of the genetic causes of CKD; establish better diagnostic methods in CKD; improve understanding of the natural course of CKD; assess and implement established treatment options in patients with CKD; improve management of symptoms and complications of CKD; develop novel therapeutic interventions to slow CKD progression and reduce CKD complications; and increase the quantity and quality of clinical trials in CKD. Each group produced a prioritised list of goals, activities, and a set of key deliverable objectives for each of the themes. The intended users of this action plan are clinicians, patients, scientists, industry partners, governments, and advocacy organisations. Implementation of this integrated comprehensive plan will benefit people who are at risk for or affected by CKD worldwide.
Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on disease morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited more than 8700 times in the literature (including citations of all annual versions). In 2009 alone, the various Statistical Updates were cited ≈1600 times (data from ISI Web of Science). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas. For this year's edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year and added a new chapter detailing how family history and genetics play a role in cardiovascular disease (CVD) risk. Also, the 2011 Statistical Update is a major source for monitoring both cardiovascular health and disease in the population, with a focus on progress toward achievement of the AHA's 2020 Impact Goals. Below are a few highlights from this year's Update.
To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. ; To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis. ; Academy of Finland 77299 102318 110413 118065 123885 124243 129680 129293 129494 136895 139635 141005 213506 251217 Agence Nationale de la Recherche (France) American Diabetes Association 7-08-MN-OK Association Francaise des Diabetiques Association de Langue Francaise pour l'Etude du Diabete et des Maladies Metaboliques (France) Association Diabete Risque Vasculaire (France) British Diabetic Association (BDA) Research (UK) British Heart Foundation RG/98002 RG2008/08 Cancer Research UK Central Norway Health Authority Central Finland Hospital District Center for Inherited Disease Research (CIDR) (USA) Chief Scientist Office, Scotland CZB/4/672 City of Kuopio (Finland) City of Leutkirch (Germany) Department of Health (UK) Deutsche Forschungsgemeinschaft ER1 55/6-2 Diabetes UK Doris Duke Charitable Foundation (USA) Estonian government SF0180142s0 European Commission: ENGAGE HEALTH-F4-2007-201413 EXGENESIS LSHM-CT-2004-005272 245536 QLG1-CT-2002-00896 2004310 European Commission (Marie Curie: FP7-PEOPLE-IEF) European Regional Development Fund Faculty of Medicine at the Norwegian University of Science and Technology Finnish Diabetes Association Finnish Diabetes Research Foundation Finnish ...
HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10−8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples. ; 3C. Three-City Study. The work was made possible by the participation of the control subjects, the patients, and their families. We thank Dr. Anne Boland (CNG) for her technical help in preparing the DNA samples for analyses. This work was supported by the National Foundation for Alzheimer's disease and related disorders, the Institut Pasteur de Lille and the Centre National de Génotypage. The 3C Study was performed as part of a collaboration between the Institut National de la Santé et de la Recherche Médicale (Inserm), the Victor Segalen Bordeaux II University and Sanofi-Synthélabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also funded by the Caisse Nationale Maladie des Travailleurs Salariés, Direction Générale de la Santé, MGEN, Institut de la Longévité, Agence Française de Sécurité Sanitaire des Produits de Santé, the Aquitaine and Bourgogne Regional Councils, Fondation de France and the joint French Ministry of Research/INSERM "Cohortes et collections de données biologiques" programme. Lille Génopôle received an unconditional grant from Eisai. AGES. Age, Gene/Environment Susceptibility-Reykjavik Study. This study has been funded by NIH contract N01-AG-1-2100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00-063. The researchers are indebted to the participants for their willingness to participate in the study. ARIC. Atherosclerosis Risk in Communities study. The ARIC study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. This work as well as YL and AK were supported by the German Research Foundation (KO 3598/2-1, KO 3598/3-1 and CRC1140 A05 to AK). ASPS. Austrian Stroke Prevention Study. The research reported in this article was funded by the Austrian Science Fond (FWF) grant number P20545-P05 and P13180. The Medical University of Graz supports the databank of the ASPS. The authors thank the staff and the participants of the ASPS for their valuable contributions. We thank Birgit Reinhart for her long-term administrative commitment and Ing Johann Semmler for the technical assistance at creating the DNA-bank. BMES. Blue Mountains Eye Study. The BMES has been supported by the Australian RADGAC grant (1992- 94) and Australian National Health & Medical Research Council, Canberra Australia (Grant Nos: 974159, 211069, 991407, 457349). The GWAS studies of Blue Mountains Eye Study population are supported by the Australian National Health & Medical Research Council (Grant Nos: 512423, 475604, 529912) and the Wellcome Trust, UK (2008). EGH and JJW are funded by the Australian National Health & Medical Research Council Fellowship Schemes. CILENTO. Italian Network on Genetic Isolates – Cilento. We thank the populations of Cilento for their participation in the study. The study was supported by the Italian Ministry of Universities and CNR 36 (PON03PE_00060_7, Interomics Flagship Project), the Assessorato Ricerca Regione Campania, the Fondazione con il SUD (2011-PDR-13), and the Istituto Banco di Napoli - Fondazione to MC. COLAUS. The CoLaus authors thank Yolande Barreau, Mathieu Firmann, Vladimir Mayor, Anne-Lise Bastian, Binasa Ramic, Martine Moranville, Martine Baumer, Marcy Sagette, Jeanne Ecoffey and Sylvie Mermoud for data collection. The CoLaus study received financial contributions from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, the Swiss National Science Foundation (33CSCO- 122661, 3200BO-111361/2, 3100AO-116323/1, 310000-112552). The computations for CoLaus imputation were performed in part at the Vital-IT center for high performance computing of the Swiss Institute of Bioinformatics. We thank Vincent Mooser for his contribution to the CoLaus study. EGCUT. Estonian Genome Center University of Tartu. EGCUT received financing from FP7 grants (278913, 306031, 313010) and targeted financing from Estonian Government (SF0180142s08). EGCUT studies were covered from Infra-structure grant no. 3.2.0304.11-0312 funded mostly by the European Regional Development Fund, Center of Excellence in Genomics (EXCEGEN) and University of Tartu (SP1GVARENG). We acknowledge EGCUT technical personnel, especially Mr V. Soo and S. Smit. Data analyses were carried out in part in the High Performance Computing Center of the University of Tartu. FamHS. Family Heart Study. The FHS work was supported in part by NIH grants 5R01HL08770003, 5R01HL08821502 (Michael A. Province) from the NHLBI and 5R01DK07568102, 5R01DK06833603 from the NIDDK (I.B.B.). The authors thank the staff and participants of the FamHS for their important contributions. FHS. Framingham Heart Study. This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham Heart Study investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (Contract No. N02-HL-6-4278). A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. GENDIAN. GENetics of DIAbetic Nephropathy study. The support of the physicians, the patients, and the staff of the Diabetes Zentrum Mergentheim (Head: Prof. Dr. Thomas Haak), the diabetes outpatient clinic Dr Nusser - Dr Kreisel, the dialysis centers KfH Amberg, KfH Bayreuth, KfH Deggendorf, KfH Donauwörth, KfH Freising, KfH Freyung, KfH Fürth, KfH Hof, KfH Ingolstadt, KfH Kelheim, KfH München Elsenheimerstraße, KfH München-Schwabing, KfH Neumarkt, KfH Neusäß, KfH Oberschleißheim, KfH Passau, KfH Plauen, KfH Regensburg Günzstraße, KfH Regensburg Caritas-Krankenhaus, KfH Straubing, KfH Sulzbach-Rosenberg, KfH Weiden, Dialysezentrum Augsburg Dr. Kirschner, Dialysezentrum Bad Alexandersbad, KfH Bamberg, Dialysezentrum Emmering, Dialysezentrum Klinikum Landshut, Dialysezentrum Landshut, Dialysezentrum Pfarrkirchen, Dialysezentrum Schwandorf, Dr. Angela Götz, the medical doctoral student Johanna Christ and the Study Nurse Ingrid Lugauer. The expert technical assistance of Claudia Strohmeier is acknowledged. Phenotyping was funded by the Dr. Robert PflegerStiftung (Dr Carsten A. Böger), the MSD Stipend Diabetes (Dr Carsten A. Böger) and the University Hospital of Regensburg (intramural grant ReForM A to Dr. A. Götz, ReForM C to Dr. Carsten Böger). Genome-wide genotyping was funded by the KfH Stiftung Präventivmedizin e.V. (Dr. Carsten A. Böger, Dr. Jens Brüning), the Else Kröner-Fresenius-Stiftung (2012_A147 to Dr Carsten A. Böger and Dr Iris M. Heid) and the University Hospital Regensburg (Dr Carsten A. Böger). Data analysis was funded by the Else 37 Kröner-Fresenius Stiftung (Dr. Iris M. Heid and Dr. Carsten A. Böger: 2012_A147; Dr. Carsten A. Böger and Dr. Bernhard K. Krämer: P48/08//A11/08). GENDIAN Study Group: Mathias Gorski, Iris M. Heid, Bernhard K. Krämer, Myriam Rheinberger, Michael Broll, Alexander Lammert, Jens Brüning, Matthias Olden, Klaus Stark, Claudia Strohmeier, Simone Neumeier, Sarah Hufnagel, Petra Jackermeier, Emilia Ruff, Johanna Christ, Peter Nürnberg, Thomas Haak, Carsten A. Böger. HABC. Health Aging and Body Composition Study. The HABC study was funded by the National Institutes of Aging. This research was supported by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. HCS. Hunter Community Study. The University of Newcastle provided $300,000 from its Strategic Initiatives Fund, and $600,000 from the Gladys M Brawn Senior Research Fellowship scheme; Vincent Fairfax Family Foundation, a private philanthropic trust, provided $195,000; The Hunter Medical Research Institute provided media support during the initial recruitment of participants; and Dr Anne Crotty, Prof. Rodney Scott and Associate Prof. Levi provided financial support towards freezing costs for the long-term storage of participant blood samples. The authors would like to thank the men and women participating in the HCS as well as all the staff, investigators and collaborators who have supported or been involved in the project to date. A special thank you should go to Alison Koschel and Debbie Quain who were instrumental in setting up the pilot study and initial phase of the project. HPFS. Health Professionals Follow-Up Study. The NHS/HPFS type 2 diabetes GWAS (U01HG004399) is a component of a collaborative project that includes 13 other GWAS (U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033; National Institute of Dental & Craniofacial Research: U01DE018993, U01DE018903) funded as part of the Gene Environment-Association Studies (GENEVA) under the NIH Genes, Environment and Health Initiative (GEI). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease"(HHSN268200782096C). Additional funding for the current research was provided by the National Cancer Institute (P01CA087969, P01CA055075), and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845). We thank the staff and participants of the NHS and HPFS for their dedication and commitment. INGI-CARLANTINO. Italian Network on Genetic Isolates – Carlantino. We thank Anna Morgan and Angela D'Eustacchio for technical support. We are grateful to the municipal administrators for their collaboration on the project and for logistic support. We thank all participants to this study. INGI-FVG. Italian Network on Genetic Isolates – Friuli Venezia-Giulia. We thank Anna Morgan and Angela D'Eustacchio for technical support. We are grateful to the municipal administrators for their collaboration on the project and for logistic support. We thank all participants to this study. 38 INGI-VAL BORBERA. Italian Network on Genetic Isolates – Val Borbera. We thank the inhabitants of the Val Borbera who made this study possible, the local administrations and the ASL-Novi Ligure (Al) for support. We also thank Clara Camaschella for data collection supervision and organization of the clinical data collection, Fiammetta Vigano` for technical help and Corrado Masciullo for building the analysis platform. The research was supported by funds from Compagnia di San Paolo, Torino, Italy; Fondazione Cariplo, Italy and Ministry of Health, Ricerca Finalizzata 2008 and 2011/2012, CCM 2010, PRIN 2009 and Telethon, Italy to DT. IPM. Mount Sinai BioMe Biobank Program. The Mount Sinai BioMe Biobank Program is supported by The Andrea and Charles Bronfman Philanthropies. KORA-F3 and F4. The genetic epidemiological work was funded by the NIH subcontract from the Children's Hospital, Boston, US, (H.E.W., I.M.H, prime grant 1 R01 DK075787-01A1), the German National Genome Research Net NGFN2 and NGFNplus (H.E.W. 01GS0823; WK project A3, number 01GS0834), the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ, and by the Else KrönerFresenius-Stiftung (P48/08//A11/08; C.A.B., B.K.K; 2012_A147 to CAB and IMH.). The Genetic Epidemiology at the University of Regensburg received financial contributions from the BMBF (01ER1206 and 01ER1507). The kidney parameter measurements in F3 were funded by the Else Kröner-FreseniusStiftung (C.A.B., B.K.K.) and the Regensburg University Medical Center, Germany; in F4 by the University of Ulm, Germany (W.K.). Genome wide genotyping costs in F3 and F4 were in part funded by the Else Kröner-Fresenius-Stiftung (C.A.B., B.K.K.). De novo genotyping in F3 and F4 were funded by the Else Kröner-Fresenius-Stiftung (C.A.B., B.K.K.). The KORA research platform and the MONICA Augsburg studies were initiated and financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, by the German Federal Ministry of Education and Research and by the State of Bavaria. Genotyping was performed in the Genome Analysis Center (GAC) of the Helmholtz Zentrum München. The LINUX platform for computation were funded by the University of Regensburg for the Department of Epidemiology and Preventive Medicine at the Regensburg University Medical Center. LIFELINES. The authors wish to acknowledge the services of the Lifelines Cohort Study, the contributing research centers delivering data to Lifelines, and all the study participants. Lifelines group authors: Behrooz Z Alizadeh1 , H Marike Boezen1 , Lude Franke2 , Pim van der Harst3 , Gerjan Navis4 , Marianne Rots5 , Harold Snieder1 , Morris Swertz2 , Bruce HR Wolffenbuttel6 and Cisca Wijmenga2 1. Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands 2. Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands 3. Department of Cardiology, University of Groningen, University Medical Center Groningen, The Netherlands 4. Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, The Netherlands 5. Department of Medical Biology, University of Groningen, University Medical Center Groningen, The Netherlands 6. Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands MESA. Multi-Ethnic Study of Atherosclerosis. University of Washington (N01-HC-95159),Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University 39 (N01-HC-95162, N01-HC-95168), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Harbor-UCLA Research and Education Institute (N01-HC- 95169), Cedars-Sinai Medical Center (R01-HL-071205), University of Virginia (subcontract to R01-HL- 071205) MICROS. Microisolates in South Tyrol study. We owe a debt of gratitude to all participants. We thank the primary care practitioners R. Stocker, S. Waldner, T. Pizzecco, J. Plangger, U. Marcadent and the personnel of the Hospital of Silandro (Department of Laboratory Medicine) for their participation and collaboration in the research project. In South Tyrol, the study was supported by the Ministry of Health and Department of Educational Assistance, University and Research of the Autonomous Province of Bolzano, the South Tyrolean Sparkasse Foundation, and the European Union framework program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). NESDA. The Netherlands Study of Depression and Anxiety. The infrastructure for the NESDA study is funded through the Geestkracht programme of the Dutch Scientific Organization (ZON-MW, grant number 10-000-1002) and matching funds from participating universities and mental health care organizations. Genotyping in NESDA was funded by the Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health. NHS. Nurses' Health Study. The NHS/HPFS type 2 diabetes GWAS (U01HG004399) is a component of a collaborative project that includes 13 other GWAS (U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, U01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, RFAHG006033; National Institute of Dental & Craniofacial Research: U01DE018993, U01DE018903) funded as part of the Gene Environment-Association Studies (GENEVA) under the NIH Genes, Environment and Health Initiative (GEI). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease"(HHSN268200782096C). The NHS renal function and albuminuria work was supported by DK66574. Additional funding for the current research was provided by the National Cancer Institute (P01CA087969, P01CA055075), and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK058845). We thank the staff and participants of the NHS and HPFS for their dedication and commitment. NSPHS. The Northern Swedish Population Health Study. The NSPHS was supported by grants from the Swedish Natural Sciences Research Council, the European Union through the EUROSPAN project (contract no. LSHG-CT-2006-018947), the Foundation for Strategic Research (SSF) and the Linneaus Centre for Bioinformatics (LCB). We are also grateful for the contribution of samples from the Medical Biobank in Umeå and for the contribution of the district nurse Svea Hennix in the Karesuando study. RS-I. The Rotterdam Study. The GWA study was funded by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA) project nr. 050-060-810. We thank Pascal Arp, Mila Jhamai, Dr Michael 40 Moorhouse, Marijn Verkerk, and Sander Bervoets for their help in creating the GWAS database. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are very grateful to the participants and staff from the Rotterdam Study, the participating general practitioners and the pharmacists. We would like to thank Dr. Tobias A. Knoch, Luc V. de Zeeuw, Anis Abuseiris, and Rob de Graaf as well as their institutions the Erasmus Computing Grid, Rotterdam, The Netherlands, and especially the national German MediGRID and Services@MediGRID part of the German D-Grid, both funded by the German Bundesministerium fuer Forschung und Technology under grants #01 AK 803 A-H and # 01 IG 07015 G, for access to their grid resources. Abbas Dehghan is supported by NWO grant (vici, 918-76-619). SAPALDIA. Swiss Study on Air Pollution and Lung Diseases in Adults. The SAPALDIA Team: Study directorate: T Rochat (p), NM Probst Hensch (e/g), N Künzli (e/exp), C Schindler (s), JM Gaspoz (c) Scientific team: JC Barthélémy (c), W Berger (g), R Bettschart (p), A Bircher (a), O Brändli (p), C Brombach (n), M Brutsche (p), L Burdet (p), M Frey (p), U Frey (pd), MW Gerbase (p), D Gold (e/c/p), E de Groot (c), W Karrer (p), R Keller (p), B Martin (pa), D Miedinger (o), U Neu (exp), L Nicod (p), M Pons (p), F Roche (c), T Rothe (p), E Russi (p), P Schmid-Grendelmeyer (a), A Schmidt-Trucksäss (pa), A Turk (p), J Schwartz (e), D. Stolz (p), P Straehl (exp), JM Tschopp (p), A von Eckardstein (cc), E Zemp Stutz (e). Scientific team at coordinating centers: M Adam (e/g), C Autenrieth (pa), PO Bridevaux (p), D Carballo (c), E Corradi (exp), I Curjuric (e), J Dratva (e), A Di Pasquale (s), E Dupuis Lozeron (s), E Fischer (e), M Germond (s), L Grize (s), D Keidel (s), S Kriemler (pa), A Kumar (g), M Imboden (g), N Maire (s), A Mehta (e), H Phuleria (exp), E Schaffner (s), GA Thun (g) A Ineichen (exp), M Ragettli (e), M Ritter (exp), T Schikowski (e), M Tarantino (s), M Tsai (exp) (a) allergology, (c) cardiology, (cc) clinical chemistry, (e) epidemiology, (exp) exposure, (g) genetic and molecular biology, (m) meteorology, (n) nutrition, (o) occupational health, (p) pneumology, (pa) physical activity, (pd) pediatrics, (s) statistics. Funding: The Swiss National Science Foundation (grants no 33CSCO-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO- 104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099), the Federal Office for Forest, Environment and Landscape, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League, the canton's Lung League of Basel Stadt/ Basel Landschaft, Geneva, Ticino, Valais and Zurich, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA. The study could not have been done without the help of the study participants, technical and administrative support and the medical teams and field workers at the local study sites. Local fieldworkers : Aarau: S Brun, G Giger, M Sperisen, M Stahel, Basel: C Bürli, C Dahler, N Oertli, I Harreh, F Karrer, G Novicic, N Wyttenbacher, Davos: A Saner, P Senn, R Winzeler, Geneva: F Bonfils, B Blicharz, C Landolt, J Rochat, Lugano: S Boccia, E Gehrig, MT Mandia, G Solari, B Viscardi, Montana: AP Bieri, C Darioly, M Maire, Payerne: F Ding, P Danieli A Vonnez, Wald: D Bodmer, E Hochstrasser, R Kunz, C Meier, J Rakic, U Schafroth, A Walder. Administrative staff: C Gabriel, R Gutknecht. SHIP and SHIP-TREND. The Study of Health in Pomerania. SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network 41 'Greifswald Approach to Individualized Medicine (GANI_MED)' funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the 'Center of Knowledge Interchange' program of the Siemens AG and the Caché Campus program of the InterSystems GmbH. The SHIP authors are grateful to Mario Stanke for the opportunity to use his Server Cluster for the SNP imputation as well as to Holger Prokisch and Thomas Meitinger (Helmholtz Zentrum München) for the genotyping of the SHIP-TREND cohort. TRAILS. TRacking Adolescents' Individual Lives. Trails is a collaborative project involving various departments of the University Medical Center and University of Groningen, the Erasmus University Medical Center Rotterdam, the University of Utrecht, the Radboud Medical Center Nijmegen, and the Parnassia Bavo group, all in the Netherlands. TRAILS has been financially supported by grants from the Netherlands Organization for Scientific Research NWO (Medical Research Council program grant GB-MW 940-38-011; ZonMW Brainpower grant 100-001-004; ZonMw Risk Behavior and Dependence grants 60- 60600-98-018 and 60-60600-97-118; ZonMw Culture and Health grant 261-98-710; Social Sciences Council medium-sized investment grants GB-MaGW 480-01-006 and GB-MaGW 480-07-001; Social Sciences Council project grants GB-MaGW 457-03-018, GB-MaGW 452-04-314, and GB-MaGW 452-06- 004; NWO large-sized investment grant 175.010.2003.005; NWO Longitudinal Survey and Panel Funding 481-08-013); the Sophia Foundation for Medical Research (projects 301 and 393), the Dutch Ministry of Justice (WODC), the European Science Foundation (EuroSTRESS project FP-006), and the participating universities. We are grateful to all adolescents, their parents and teachers who participated in this research and to everyone who worked on this project and made it possible. Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003) along with a supplement from the Dutch Brain Foundation. WGHS. Women's Genome Health Study. The WGHS is supported by the National Heart, Lung, and Blood Institute (HL043851 and HL080467) and the National Cancer Institute (CA047988 and UM1CA182913), with collaborative scientific support and funding for genotyping provided by Amgen. YFS. Young Finns Study. The YFS has been financially supported by the Academy of Finland: grants 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi), the Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds (grant 9M048 and 9N035 for TeLeht), Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation, Tampere Tuberculosis Foundation and Emil Aaltonen Foundation (T.L). The technical assistance in the statistical analyses by Ville Aalto and Irina Lisinen is acknowledged. ; Peer Reviewed
Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery. ; The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (102318; 104781, 120315, 123885, 129619, 286284, 134309, 126925, 121584, 124282, 129378, 117787, 250207, 258753, 41071, 77299, 124243, 1114194, 24300796); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la Recherche; Agency for Health Care Policy Research (HS06516); Age UK Research into Ageing Fund; Åke Wiberg Foundation; ALF/LUA Research Grant in Gothenburg; ALFEDIAM; ALK-Abello´ A/S (Hørsholm, Denmark); American Heart Association (13POST16500011, 10SDG269004); Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; AstraZeneca; Australian Associated Brewers; Australian National Health and Medical Research Council (241944, 339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498); Avera Research Institute; Bayer Diagnostics; Becton Dickinson; Biobanking and Biomolecular Resources Research Infrastructure (BBMRI –NL, 184.021.007); Biocentrum Helsinki; Boston Obesity Nutrition Research Center (DK46200); British Heart Foundation (RG/10/12/28456, SP/04/002); Canada Foundation for Innovation; Canadian Institutes of Health Research (FRN-CCT-83028); Cancer Research UK; Cardionics; Center for Medical Systems Biology; Center of Excellence in Complex Disease Genetics and SALVECenter of Excellence in Genomics (EXCEGEN); Chief Scientist Office of the Scottish Government; City of Kuopio; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF–1333-00124, DFF–1331-007308); Danish Diabetes Academy; Danish Medical Research Council; Department of Psychology and Education of the VU University Amsterdam; Diabetes Hilfs- und Forschungsfonds Deutschland; Dutch Brain Foundation; Dutch Ministry of Justice; Emil Aaltonen Foundation; Erasmus Medical Center; Erasmus University; Estonian Government (IUT20-60, IUT24-6); Estonian Ministry of Education and Research (3.2.0304.11-0312); European Commission (230374, 284167, 323195, 692145, FP7 EurHEALTHAgeing-277849, FP7 BBMRI-LPC 313010, nr 602633, HEALTH-F2-2008-201865-GEFOS, HEALTH-F4-2007-201413, FP6 LSHM-CT-2004-005272, FP5 QLG2-CT-2002-01254, FP6 LSHG-CT-2006-01947, FP7 HEALTH-F4-2007-201413, FP7 279143, FP7 201668, FP7 305739, FP6 LSHG-CT-2006-018947, HEALTH-F4-2007-201413, QLG1-CT-2001-01252); European Regional Development Fund; European Science Foundation (EuroSTRESS project FP-006, ESF, EU/QLRT-2001-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 03IS2061A); Federal State of Mecklenburg - West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Food Standards Agency; Fondation de France; Fonds Santé; Genetic Association Information Network of the Foundation for the National Institutes of Health; German Diabetes Association; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); German Research Council (SFB-1052, SPP 1629 TO 718/2-1); GlaxoSmithKline; Göran Gustafssons Foundation; Göteborg Medical Society; Health and Safety Executive; Heart Foundation of Northern Sweden; Icelandic Heart Association; Icelandic Parliament; Imperial College Healthcare NHS Trust; INSERM, Réseaux en Santé Publique, Interactions entre les déterminants de la santé; Interreg IV Oberrhein Program (A28); Italian Ministry of Economy and Finance; Italian Ministry of Health (ICS110.1/RF97.71); John D and Catherine T MacArthur Foundation; Juho Vainio Foundation; King's College London; Kjell och Märta Beijers Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); Leiden University Medical Center; Lilly; LMUinnovativ; Lundbeck Foundation; Lundberg Foundation; Medical Research Council of Canada; MEKOS Laboratories (Denmark); Merck Santé; Mid-Atlantic Nutrition Obesity Research Center (P30 DK72488); Ministère de l'Économie, de l'Innovation et des Exportations; Ministry for Health, Welfare and Sports of the Netherlands; Ministry of Cultural Affairs of the Federal State of Mecklenburg-West Pomerania; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science of the Netherlands; MRC Human Genetics Unit; MRC-GlaxoSmithKline Pilot Programme Grant (G0701863); Municipality of Rotterdam; Netherlands Bioinformatics Centre (2008.024); Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Genomics Initiative; Netherlands Organisation for Health Research and Development (904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie 56-464-14192); Netherlands Organisation for Health Research and Development (2010/31471/ZONMW); Netherlands Organisation for Scientific Research (10-000-1002, GB-MW 940-38-011, 100-001-004, 60-60600-97-118, 261-98-710, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MaGW 452-04-314, GB-MaGW 452-06-004, 175.010.2003.005, 175.010.2005.011, 481-08-013, 480-05-003, 911-03-012); Neuroscience Campus Amsterdam; NHS Foundation Trust; Novartis Pharmaceuticals; Novo Nordisk; Office National Interprofessionel des Vins; Paavo Nurmi Foundation; Påhlssons Foundation; Päivikki and Sakari Sohlberg Foundation; Pierre Fabre; Republic of Croatia Ministry of Science, Education and Sport (108-1080315-0302); Research Centre for Prevention and Health, the Capital Region for Denmark; Research Institute for Diseases in the Elderly (014-93-015, RIDE2); Roche; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Executive Health Department (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du Diabète; State of Bavaria; Stroke Association; Swedish Diabetes Association; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20140543); Swedish Research Council (2015-03657); Swedish Medical Research Council (K2007-66X-20270-01-3, 2011-2354); Swedish Society for Medical Research; Swiss National Science Foundation (33CSCO-122661, 33CS30-139468, 33CS30-148401); Tampere Tuberculosis Foundation; The Marcus Borgström Foundation; The Royal Society; The Wellcome Trust (084723/Z/08/Z, 088869/B/09/Z); Timber Merchant Vilhelm Bangs Foundation; Topcon; Torsten and Ragnar Söderberg's Foundation; UK Department of Health; UK Diabetes Association; UK Medical Research Council (MC_U106179471, G0500539, G0600705, G0601966, G0700931, G1002319, K013351, MC_UU_12019/1); UK National Institute for Health Research BioResource Clinical Research Facility and Biomedical Research Centre; UK National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre; UK National Institute for Health Research (RP-PG-0407-10371); Umeå University Career Development Award; United States – Israel Binational Science Foundation Grant (2011036); University Hospital Oulu (75617); University Medical Center Groningen; University of Tartu (SP1GVARENG); National Institutes of Health (AG13196, CA047988, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSC271201100004C, HHSN268200900041C, HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, HHSN268201500001I, HL36310, HG002651, HL034594, HL054457, HL054481, HL071981, HL084729, HL119443, HL126024, N01-AG12100, N01-AG12109, N01-HC25195, N01-HC55015, N01-HC55016, N01-HC55018, N01-HC55019, N01-HC55020, N01-HC55021, N01-HC55022, N01-HD95159, N01-HD95160, N01-HD95161, N01-HD95162, N01-HD95163, N01-HD95164, N01-HD95165, N01-HD95166, N01-HD95167, N01-HD95168, N01-HD95169, N01-HG65403, N02-HL64278, R01-HD057194, R01-HL087641, R01-HL59367, R01HL-086694, R01-HL088451, R24-HD050924, U01-HG-004402, HHSN268200625226C, UL1-RR025005, UL1-RR025005, UL1-TR-001079, UL1-TR-00040, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, DA12854, MH081802, MH66206, R01-D004215701A, R01-DK075787, R01-DK089256, R01-DK8925601, R01-HL088451, R01-HL117078, R01-DK062370, R01-DK072193, DK091718, DK100383, DK078616, 1Z01-HG000024, HL087660, HL100245, R01DK089256, 2T32HL007055-36, U01-HL072515-06, U01-HL84756, NIA-U01AG009740, RC2-AG036495, RC4-AG039029, R03 AG046389, 263-MA-410953, 263-MD-9164, 263-MD-821336, U01-HG004802, R37CA54281, R01CA63, P01CA33619, U01-CA136792, U01-CA98758, RC2-MH089951, MH085520, R01-D0042157-01A, MH081802, 1RC2-MH089951, 1RC2-MH089995, 1RL1MH08326801, U01-HG007376, 5R01-HL08767902, 5R01MH63706:02, HG004790, N01-WH22110, U01-HG007033, UM1CA182913, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221); USDA National Institute of Food and Agriculture (2007-35205-17883); Västra Götaland Foundation; Velux Foundation; Veterans Affairs (1 IK2 BX001823); Vleugels Foundation; VU University's Institute for Health and Care Research (EMGO+, HEALTH-F4-2007-201413) and Neuroscience Campus Amsterdam; Wellcome Trust (090532, 091551, 098051, 098381); Wissenschaftsoffensive TMO; and Yrjö Jahnsson Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Peer Reviewed
Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution. ; A full list of acknowledgments appears in the Supplementary Note 4. Co-author A.J.M.d.C. recently passed away while this work was in process. This work was performed under the auspices of the Genetic Investigation of ANthropometric Traits (GIANT) consortium. We acknowledge the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium for encouraging CHARGE studies to participate in this effort and for the contributions of CHARGE members to the analyses conducted for this research. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (41071, 77299, 102318, 110413, 117787, 121584, 123885, 124243, 124282, 126925, 129378, 134309, 286284); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la 359 Recherche; Agency for Health Care Policy Research (HS06516); ALF/LUA research grant in Gothenburg; ALFEDIAM; ALK-Abelló A/S; Althingi; American Heart Association (13POST16500011); Amgen; Andrea and Charles Bronfman Philanthropies; Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; Australian National Health and Medical Research Council (241944, 339462, 389875, 389891, 389892, 389927, 389938, 442915, 442981, 496739, 552485, 552498); Avera Institute; Bayer Diagnostics; Becton Dickinson; BHF (RG/14/5/30893); Boston Obesity Nutrition Research Center (DK46200), Bristol-Myers Squibb; British Heart Foundation (RG/10/12/28456, RG2008/08, RG2008/014, SP/04/002); Medical Research Council of Canada; Canadian Institutes for Health Research (FRCN-CCT-83028); Cancer Research UK; Cardionics; Cavadis B.V., Center for Medical Systems Biology; Center of Excellence in Genomics; CFI; CIHR; City of Kuopio; CNAMTS; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF-1333-00124, DFF-1331-00730B); County Council of Dalarna; Dalarna University; Danish Council for Strategic Research; Danish Diabetes Academy; Danish Medical Research Council; Department of Health, UK; Development Fund from the University of Tartu (SP1GVARENG); Diabetes Hilfs- und Forschungsfonds Deutschland; Diabetes UK; Diabetes Research and Wellness Foundation Fellowship; Donald W. Reynolds Foundation; Dr Robert Pfleger-Stiftung; Dutch Brain Foundation; Dutch Diabetes Research Foundation; Dutch Inter University Cardiology Institute; Dutch Kidney Foundation (E033); Dutch Ministry of Justice; the DynaHEALTH action No. 633595, Economic Structure Enhancing Fund of the Dutch Government; Else Kröner-Fresenius-Stiftung (2012_A147, P48/08//A11/08); Emil Aaltonen Foundation; Erasmus University Medical Center Rotterdam; Erasmus MC and Erasmus University Rotterdam; the Municipality of Rotterdam; Estonian Government (IUT20-60, IUT24-6); Estonian Research Roadmap through the Estonian Ministry of Education and Research (3.2.0304.11-0312); European Research Council (ERC Starting Grant and 323195:SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC); European Regional Development Fund; European Science Foundation (EU/QLRT-2001-01254); European Commission (018947, 018996, 201668, 223004, 230374, 279143, 284167, 305739, BBMRI-LPC-313010, HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-2011-278913, HEALTH-2011-294713-EPLORE, HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2013-601456, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550-HYPERGENES, HEALTH-F7-305507 HOMAGE, IMI/115006, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHM-CT-2004-005272, LSHM-CT-2006-037697, LSHM-CT-2007-037273, QLG1-CT-2002-00896, QLG2-CT-2002-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ0103, 01ZZ0403, 01ZZ9603, 03IS2061A, 03ZIK012); Federal State of Mecklenburg-West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Fondation Leducq; Food Standards Agency; Foundation for Strategic Research; French Ministry of Research; FRSQ; Genetic Association Information Network (GAIN) of the Foundation for the NIH; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); GlaxoSmithKline; Greek General Secretary of Research and Technology; Göteborg Medical Society; Health and Safety Executive; Healthcare NHS Trust; Healthway; Western Australia; Heart Foundation of Northern Sweden; Helmholtz Zentrum München—German Research Center for Environmental Health; Hjartavernd; Ingrid Thurings Foundation; INSERM; InterOmics (PB05 MIUR-CNR); INTERREG IV Oberrhein Program (A28); Interuniversity Cardiology Institute of the Netherlands (ICIN, 09.001); Italian Ministry of Health (ICS110.1/RF97.71); Italian Ministry of Economy and Finance (FaReBio di Qualità); Marianne and Marcus Wallenberg Foundation; the Ministry of Health, Welfare and Sports, the Netherlands; J.D.E. and Catherine T, MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International; KfH Stiftung Präventivmedizin e.V.; King's College London; Knut and Alice Wallenberg Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); La Fondation de France; Leenaards Foundation; Lilly; LMUinnovativ; Lundberg Foundation; Magnus Bergvall Foundation; MDEIE; Medical Research Council UK (G0000934, G0601966, G0700931, MC_U106179471, MC_UU_12019/1); MEKOS Laboratories; Merck Santé; Ministry for Health, Welfare and Sports, The Netherlands; Ministry of Cultural Affairs of Mecklenburg-West Pomerania; Ministry of Economic Affairs, The Netherlands; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science, The Netherlands; Ministry of Science, Education and Sport in the Republic of Croatia (108-1080315-0302); MRC centre for Causal Analyses in Translational Epidemiology; MRC Human Genetics Unit; MRC-GlaxoSmithKline pilot programme (G0701863); MSD Stipend Diabetes; National Institute for Health Research; Netherlands Brain Foundation (F2013(1)-28); Netherlands CardioVascular Research Initiative (CVON2011-19); Netherlands Genomics Initiative (050-060-810); Netherlands Heart Foundation (2001 D 032, NHS2010B280); Netherlands Organization for Scientific Research (NWO) and Netherlands Organisation for Health Research and Development (ZonMW) (56-464-14192, 60-60600-97-118, 100-001-004, 261-98-710, 400-05-717, 480-04-004, 480-05-003, 481-08-013, 904-61-090, 904-61-193, 911-11-025, 985-10-002, Addiction-31160008, BBMRI–NL 184.021.007, GB-MaGW 452-04-314, GB-MaGW 452-06-004, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MW 940-38-011, Middelgroot-911-09-032, NBIC/BioAssist/RK 2008.024, Spinozapremie 175.010.2003.005, 175.010.2007.006); Neuroscience Campus Amsterdam; NHS Foundation Trust; National Institutes of Health (1RC2MH089951, 1Z01HG000024, 24152, 263MD9164, 263MD821336, 2R01LM010098, 32100-2, 32122, 32108, 5K99HL130580-02, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, AG13196, CA047988, DA12854, DK56350, DK063491, DK078150, DK091718, DK100383, DK078616, ES10126, HG004790, HHSN268200625226C, HHSN268200800007C, HHSN268201200036C, HHSN268201500001I, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, HL043851, HL45670, HL080467, HL085144, HL087660, HL054457, HL119443, HL118305, HL071981, HL034594, HL126024, HL130114, KL2TR001109, MH66206, MH081802, N01AG12100, N01HC55015, N01HC55016, N01C55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC95159, N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169, N01HG65403, N01WH22110, N02HL6‐4278, N01-HC-25195, P01CA33619, R01HD057194, R01HD057194, R01AG023629, R01CA63, R01D004215701A, R01DK075787, R01DK062370, R01DK072193, R01DK075787, R01DK089256, R01HL53353, R01HL59367, R01HL086694, R01HL087641, R01HL087652, R01HL103612, R01HL105756, R01HL117078, R01HL120393, R03 AG046389, R37CA54281, RC2AG036495, RC4AG039029, RPPG040710371, RR20649, TW008288, TW05596, U01AG009740, U01CA98758, U01CA136792, U01DK062418, U01HG004402, U01HG004802, U01HG007376, U01HL080295, UL1RR025005, UL1TR000040, UL1TR000124, UL1TR001079, 2T32HL007055-36, T32GM074905, HG002651, HL084729, N01-HC-25195, UM1CA182913); NIH, National Institute on Aging (Intramural funding, NO1-AG-1-2109); Northern Netherlands Collaboration of Provinces; Novartis Pharma; Novo Nordisk; Novo Nordisk Foundation; Nutricia Research Foundation (2016-T1); ONIVINS; Parnassia Bavo group; Pierre Fabre; Province of Groningen; Päivikki and Sakari Sohlberg Foundation; Påhlssons Foundation; Paavo Nurmi Foundation; Radboud Medical Center Nijmegen; Research Centre for Prevention and Health, the Capital Region of Denmark; the Research Institute for Diseases in the Elderly; Research into Ageing; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Roche; Royal Society; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Government Health Directorates, Chief Scientist Office (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du 358 Diabète; State of Bavaria; Stiftelsen för Gamla Tjänarinnor; Stockholm County Council (560183, 592229); Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council; Stroke Association; Swedish Diabetes Association; Swedish Diabetes Foundation (2013-024); Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20120197, 20150711); Swedish Research Council (0593, 8691, 2012-1397, 2012-1727, and 2012-2215); Swedish Society for Medical Research; Swiss Institute of Bioinformatics; Swiss National Science Foundation (3100AO-116323/1, 31003A-143914, 33CSCO-122661, 33CS30-139468, 33CS30-148401, 51RTP0_151019); Tampere Tuberculosis Foundation; Technology Foundation STW (11679); The Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community (G.0880.13, G.0881.13); The Great Wine Estates of the Margaret River Region of Western Australia; Timber Merchant Vilhelm Bangs Foundation; Topcon; Tore Nilsson Foundation; Torsten and Ragnar Söderberg's Foundation; United States – Israel Binational Science Foundation (Grant 2011036), Umeå University; University Hospital of Regensburg; University of Groningen; University Medical Center Groningen; University of Michigan; University of Utrecht; Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) (b2011036); Velux Foundation; VU University's Institute for Health and Care Research; Västra Götaland Foundation; Wellcome Trust (068545, 076113, 079895, 084723, 088869, WT064890, WT086596, WT098017, WT090532, WT098051, 098381); Wissenschaftsoffensive TMO; Yrjö Jahnsson Foundation; and Åke Wiberg Foundation. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute (NHLBI); the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services. ; Peer Reviewed
Acknowledgements A full list of acknowledgments appears in the Supplementary Note 4. Co-author A.J.M.d.C. recently passed away while this work was in process. This work was performed under the auspices of the Genetic Investigation of ANthropometric Traits (GIANT) consortium. We acknowledge the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium for encouraging CHARGE studies to participate in this effort and for the contributions of CHARGE members to the analyses conducted for this research. Funding for this study was provided by the Aase and Ejner Danielsens Foundation; Academy of Finland (41071, 77299, 102318, 110413, 117787, 121584, 123885, 124243, 124282, 126925, 129378, 134309, 286284); Accare Center for Child and Adolescent Psychiatry; Action on Hearing Loss (G51); Agence Nationale de la 359 Recherche; Agency for Health Care Policy Research (HS06516); ALF/LUA research grant in Gothenburg; ALFEDIAM; ALK-Abelló A/S; Althingi; American Heart Association (13POST16500011); Amgen; Andrea and Charles Bronfman Philanthropies; Ardix Medical; Arthritis Research UK; Association Diabète Risque Vasculaire; Australian National Health and Medical Research Council (241944, 339462, 389875, 389891, 389892, 389927, 389938, 442915, 442981, 496739, 552485, 552498); Avera Institute; Bayer Diagnostics; Becton Dickinson; BHF (RG/14/5/30893); Boston Obesity Nutrition Research Center (DK46200), Bristol-Myers Squibb; British Heart Foundation (RG/10/12/28456, RG2008/08, RG2008/014, SP/04/002); Medical Research Council of Canada; Canadian Institutes for Health Research (FRCN-CCT-83028); Cancer Research UK; Cardionics; Cavadis B.V., Center for Medical Systems Biology; Center of Excellence in Genomics; CFI; CIHR; City of Kuopio; CNAMTS; Cohortes Santé TGIR; Contrat de Projets État-Région; Croatian Science Foundation (8875); Danish Agency for Science, Technology and Innovation; Danish Council for Independent Research (DFF-1333-00124, DFF-1331-00730B); County Council of Dalarna; Dalarna University; Danish Council for Strategic Research; Danish Diabetes Academy; Danish Medical Research Council; Department of Health, UK; Development Fund from the University of Tartu (SP1GVARENG); Diabetes Hilfs- und Forschungsfonds Deutschland; Diabetes UK; Diabetes Research and Wellness Foundation Fellowship; Donald W. Reynolds Foundation; Dr Robert Pfleger-Stiftung; Dutch Brain Foundation; Dutch Diabetes Research Foundation; Dutch Inter University Cardiology Institute; Dutch Kidney Foundation (E033); Dutch Ministry of Justice; the DynaHEALTH action No. 633595, Economic Structure Enhancing Fund of the Dutch Government; Else Kröner-Fresenius-Stiftung (2012_A147, P48/08//A11/08); Emil Aaltonen Foundation; Erasmus University Medical Center Rotterdam; Erasmus MC and Erasmus University Rotterdam; the Municipality of Rotterdam; Estonian Government (IUT20-60, IUT24-6); Estonian Research Roadmap through the Estonian Ministry of Education and Research (3.2.0304.11-0312); European Research Council (ERC Starting Grant and 323195:SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC); European Regional Development Fund; European Science Foundation (EU/QLRT-2001-01254); European Commission (018947, 018996, 201668, 223004, 230374, 279143, 284167, 305739, BBMRI-LPC-313010, HEALTH-2011.2.4.2-2-EU-MASCARA, HEALTH-2011-278913, HEALTH-2011-294713-EPLORE, HEALTH-F2-2008-201865-GEFOS, HEALTH-F2-2013-601456, HEALTH-F4-2007-201413, HEALTH-F4-2007-201550-HYPERGENES, HEALTH-F7-305507 HOMAGE, IMI/115006, LSHG-CT-2006-018947, LSHG-CT-2006-01947, LSHM-CT-2004-005272, LSHM-CT-2006-037697, LSHM-CT-2007-037273, QLG1-CT-2002-00896, QLG2-CT-2002-01254); Faculty of Biology and Medicine of Lausanne; Federal Ministry of Education and Research (01ZZ0103, 01ZZ0403, 01ZZ9603, 03IS2061A, 03ZIK012); Federal State of Mecklenburg-West Pomerania; Fédération Française de Cardiologie; Finnish Cultural Foundation; Finnish Diabetes Association; Finnish Foundation of Cardiovascular Research; Finnish Heart Association; Fondation Leducq; Food Standards Agency; Foundation for Strategic Research; French Ministry of Research; FRSQ; Genetic Association Information Network (GAIN) of the Foundation for the NIH; German Federal Ministry of Education and Research (BMBF, 01ER1206, 01ER1507); GlaxoSmithKline; Greek General Secretary of Research and Technology; Göteborg Medical Society; Health and Safety Executive; Healthcare NHS Trust; Healthway; Western Australia; Heart Foundation of Northern Sweden; Helmholtz Zentrum München—German Research Center for Environmental Health; Hjartavernd; Ingrid Thurings Foundation; INSERM; InterOmics (PB05 MIUR-CNR); INTERREG IV Oberrhein Program (A28); Interuniversity Cardiology Institute of the Netherlands (ICIN, 09.001); Italian Ministry of Health (ICS110.1/RF97.71); Italian Ministry of Economy and Finance (FaReBio di Qualità); Marianne and Marcus Wallenberg Foundation; the Ministry of Health, Welfare and Sports, the Netherlands; J.D.E. and Catherine T, MacArthur Foundation Research Networks on Successful Midlife Development and Socioeconomic Status and Health; Juho Vainio Foundation; Juvenile Diabetes Research Foundation International; KfH Stiftung Präventivmedizin e.V.; King's College London; Knut and Alice Wallenberg Foundation; Kuopio University Hospital; Kuopio, Tampere and Turku University Hospital Medical Funds (X51001); La Fondation de France; Leenaards Foundation; Lilly; LMUinnovativ; Lundberg Foundation; Magnus Bergvall Foundation; MDEIE; Medical Research Council UK (G0000934, G0601966, G0700931, MC_U106179471, MC_UU_12019/1); MEKOS Laboratories; Merck Santé; Ministry for Health, Welfare and Sports, The Netherlands; Ministry of Cultural Affairs of Mecklenburg-West Pomerania; Ministry of Economic Affairs, The Netherlands; Ministry of Education and Culture of Finland (627;2004-2011); Ministry of Education, Culture and Science, The Netherlands; Ministry of Science, Education and Sport in the Republic of Croatia (108-1080315-0302); MRC centre for Causal Analyses in Translational Epidemiology; MRC Human Genetics Unit; MRC-GlaxoSmithKline pilot programme (G0701863); MSD Stipend Diabetes; National Institute for Health Research; Netherlands Brain Foundation (F2013(1)-28); Netherlands CardioVascular Research Initiative (CVON2011-19); Netherlands Genomics Initiative (050-060-810); Netherlands Heart Foundation (2001 D 032, NHS2010B280); Netherlands Organization for Scientific Research (NWO) and Netherlands Organisation for Health Research and Development (ZonMW) (56-464-14192, 60-60600-97-118, 100-001-004, 261-98-710, 400-05-717, 480-04-004, 480-05-003, 481-08-013, 904-61-090, 904-61-193, 911-11-025, 985-10-002, Addiction-31160008, BBMRI–NL 184.021.007, GB-MaGW 452-04-314, GB-MaGW 452-06-004, GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MW 940-38-011, Middelgroot-911-09-032, NBIC/BioAssist/RK 2008.024, Spinozapremie 175.010.2003.005, 175.010.2007.006); Neuroscience Campus Amsterdam; NHS Foundation Trust; National Institutes of Health (1RC2MH089951, 1Z01HG000024, 24152, 263MD9164, 263MD821336, 2R01LM010098, 32100-2, 32122, 32108, 5K99HL130580-02, AA07535, AA10248, AA11998, AA13320, AA13321, AA13326, AA14041, AA17688, AG13196, CA047988, DA12854, DK56350, DK063491, DK078150, DK091718, DK100383, DK078616, ES10126, HG004790, HHSN268200625226C, HHSN268200800007C, HHSN268201200036C, HHSN268201500001I, HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C, HL043851, HL45670, HL080467, HL085144, HL087660, HL054457, HL119443, HL118305, HL071981, HL034594, HL126024, HL130114, KL2TR001109, MH66206, MH081802, N01AG12100, N01HC55015, N01HC55016, N01C55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC95159, N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165, N01HC95166, N01HC95167, N01HC95168, N01HC95169, N01HG65403, N01WH22110, N02HL6‐4278, N01-HC-25195, P01CA33619, R01HD057194, R01HD057194, R01AG023629, R01CA63, R01D004215701A, R01DK075787, R01DK062370, R01DK072193, R01DK075787, R01DK089256, R01HL53353, R01HL59367, R01HL086694, R01HL087641, R01HL087652, R01HL103612, R01HL105756, R01HL117078, R01HL120393, R03 AG046389, R37CA54281, RC2AG036495, RC4AG039029, RPPG040710371, RR20649, TW008288, TW05596, U01AG009740, U01CA98758, U01CA136792, U01DK062418, U01HG004402, U01HG004802, U01HG007376, U01HL080295, UL1RR025005, UL1TR000040, UL1TR000124, UL1TR001079, 2T32HL007055-36, T32GM074905, HG002651, HL084729, N01-HC-25195, UM1CA182913); NIH, National Institute on Aging (Intramural funding, NO1-AG-1-2109); Northern Netherlands Collaboration of Provinces; Novartis Pharma; Novo Nordisk; Novo Nordisk Foundation; Nutricia Research Foundation (2016-T1); ONIVINS; Parnassia Bavo group; Pierre Fabre; Province of Groningen; Päivikki and Sakari Sohlberg Foundation; Påhlssons Foundation; Paavo Nurmi Foundation; Radboud Medical Center Nijmegen; Research Centre for Prevention and Health, the Capital Region of Denmark; the Research Institute for Diseases in the Elderly; Research into Ageing; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; Roche; Royal Society; Russian Foundation for Basic Research (NWO-RFBR 047.017.043); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Sanofi-Aventis; Scottish Government Health Directorates, Chief Scientist Office (CZD/16/6); Siemens Healthcare; Social Insurance Institution of Finland (4/26/2010); Social Ministry of the Federal State of Mecklenburg-West Pomerania; Société Francophone du 358 Diabète; State of Bavaria; Stiftelsen för Gamla Tjänarinnor; Stockholm County Council (560183, 592229); Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council; Stroke Association; Swedish Diabetes Association; Swedish Diabetes Foundation (2013-024); Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation (20120197, 20150711); Swedish Research Council (0593, 8691, 2012-1397, 2012-1727, and 2012-2215); Swedish Society for Medical Research; Swiss Institute of Bioinformatics; Swiss National Science Foundation (3100AO-116323/1, 31003A-143914, 33CSCO-122661, 33CS30-139468, 33CS30-148401, 51RTP0_151019); Tampere Tuberculosis Foundation; Technology Foundation STW (11679); The Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community (G.0880.13, G.0881.13); The Great Wine Estates of the Margaret River Region of Western Australia; Timber Merchant Vilhelm Bangs Foundation; Topcon; Tore Nilsson Foundation; Torsten and Ragnar Söderberg's Foundation; United States – Israel Binational Science Foundation (Grant 2011036), Umeå University; University Hospital of Regensburg; University of Groningen; University Medical Center Groningen; University of Michigan; University of Utrecht; Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX) (b2011036); Velux Foundation; VU University's Institute for Health and Care Research; Västra Götaland Foundation; Wellcome Trust (068545, 076113, 079895, 084723, 088869, WT064890, WT086596, WT098017, WT090532, WT098051, 098381); Wissenschaftsoffensive TMO; Yrjö Jahnsson Foundation; and Åke Wiberg Foundation. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute (NHLBI); the National Institutes of Health (NIH); or the U.S. Department of Health and Human Services. ; Peer reviewed ; Publisher PDF
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.