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AbstractThe genetics of asthma and atopy has been studied frequently in twin populations from various parts of the world. However, emphasis has been put on univariate analysis of questionnaire data, whereas clinical and intermediate traits only sporadically have been studied, especially in multivariate settings. This review focuses on multivariate twin studies of atopy and related traits. We conclude that the genetic liability to most atopic traits is significantly correlated but that trait-specific genes also play a role. Previous studies have estimated the genetic correlation between upper and lower respiratory allergic symptoms, that is, asthma and hay fever, to be between .47 and .95. Furthermore, atopic traits share a portion of their genetic determinants with other complex disorders like obesity and behavioral traits. A correlation of about .3 and .34 has been reported between genes associated with asthma and obesity, and between genes associated with asthma and depression, respectively. We emphasize that multivariate methods applied to twin studies, especially when genetic marker information is available, provide a valuable framework within which complex etiological mechanisms underlying atopy can be disentangled.

AbstractTwins constitute a valuable resource for genetic studies of asthma. However, critics argue that twins are 'special' in terms of prenatal environment and upbringing and therefore nonrepresentative. In respect to asthma a small range of studies report differential morbidity in twins compared with singletons. We review some of the possible explanations for these findings and conclude that results from twin studies of asthma can be extrapolated to the general population.

Acknowledgements The authors thank the following individuals who contributed to the initial set-up of ISAR, provided input to the development of the protocol and/or were involved in local implementation of ISAR: Elisabeth Bel, Roland Buhl, Sverre Lehmann, Stelios Loukidis, Richard Martin, Juno Pak, Pearlanne Zelar ney, Joy Zimmer, Christena Kolakowski, Margo Brown, Jessica Cummings, Jennifer Brandorff, Seth Skelton, John Upham, Philip Bardin, Paul Reynolds, David Langton, Peter Middleton, Belinda Cochrane, Katya Vasileva Noleva, Plamen Hristov Yakovliev, Sonya Metodieva Genova, Violina Milchova Vasi leva, Darina Petrova Dimova, Nadezhda K Takovska, Cvetantka Hristova Odz hakova, Eleonora M Stamenova, Diana X Hristova, Vincente Plaza, Ian Hirsch, Cekomir Vodenicharov, Alexandrina Vodenicharova and Magdalena Alexandrova. Medical writing support was provided by Michelle Rebello, PhD, and Liam Gillies, PhD, of Cactus Communications (Mumbai, India). Funding The International Severe Asthma Registry is conducted by Optimum Patient Care Global Limited, and co-funded by Optimum Patient Care Global Limited and AstraZeneca. ISAR is supported by grants from AstraZeneca and Optimum Patient Care (OPC) Global (a not-for-profit social enterprise). The ISAR steering committee (ISC) was involved in the development of the protocol and is responsible for approving research proposals via a democratic voting process. In addition to 47 clinicians and researchers with an interest and experience in severe asthma, the ISC also includes members of OPC and four medical experts from AstraZeneca. AstraZeneca reviewed the draft before submission; however, decision to submit was made by the authors. Medical writing support was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). ; Peer reviewed ; Publisher PDF

Publisher's version (útgefin grein) ; Background: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour. Methods: ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC; comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (=18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR's collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics and Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders. Conclusions: ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally. ; The International Severe Asthma Registry is conducted by Optimum Patient Care Global Limited, and co-funded by Optimum Patient Care Global Limited and AstraZeneca. ISAR is supported by grants from AstraZeneca and Optimum Patient Care (OPC) Global (a not-for-profit social enterprise). The ISAR steering committee (ISC) was involved in the development of the protocol and is responsible for approving research proposals via a democratic voting process. In addition to 47 clinicians and researchers with an interest and experience in severe asthma, the ISC also includes members of OPC and four medical experts from AstraZeneca. AstraZeneca reviewed the draft before submission; however, decision to submit was made by the authors. Medical writing support was funded by AstraZeneca in accordance with Good Publication Practice (GPP3) guidelines (http://www.ismpp.org/gpp3). ; Peer Reviewed