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Evaluating the contribution of genetic and familial shared environment to common disease using the UK Biobank

Maria Munoz, Ricardo Pong-Wong, Oriol Canela-Xandri, Konrad Rawlik, Christopher Haley, Albert Tenesa

Research output: Contribution to journal › Article › peer-review

Abstract

Genome-wide association studies have detected many loci underlying susceptibility to disease, but most of the genetic factors that contribute to disease susceptibility remain unknown. Here we provide evidence that part of the missing heritability can be explained by an overestimation of heritability. We estimated the heritability of twelve complex human diseases using family history of disease in 1,555,906 white European individuals from the UK Biobank. Estimates using simple family-based statistical models were inflated on average by ~47% comparing with those from Structural Equation Models (SEM) that specifically accounted for shared familial environmental factors. In addition, heritabilities using SNP data explained an average of 44.2% of the simple family-based estimates across diseases and an average of 57.3% of SEM estimated heritability and accounted for almost all of the SEM heritability for hypertension. Our results show that both genetics and familial environment make substantial contributions to familial clustering of disease.
Original languageEnglish
Pages (from-to)980-983
JournalNature Genetics
Volume48
Issue number9
Early online date18 Jul 2016
DOIs
Publication statusPublished - Sept 2016

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    • ISP1: Analysis and prediction in complex animal systems

      Tenesa, A. (Principal Investigator), Archibald, A. (Co-investigator), Beard, P. (Co-investigator), Bishop, S. (Co-investigator), Bronsvoort, M. (Co-investigator), Burt, D. (Co-investigator), Freeman, T. (Co-investigator), Haley, C. (Co-investigator), Hocking, P. (Co-investigator), Houston, R. (Co-investigator), Hume, D. (Co-investigator), Joshi, A. (Co-investigator), Law, A. (Co-investigator), Michoel, T. (Co-investigator), Summers, K. (Co-investigator), Vernimmen, D. (Co-investigator), Watson, M. (Co-investigator), Wiener, P. (Co-investigator), Wilson, A. (Co-investigator), Woolliams, J. (Co-investigator), Ait-Ali, T. (Researcher), Barnett, M. (Researcher), Carlisle, A. (Researcher), Finlayson, H. (Researcher), Haga, I. (Researcher), Karavolos, M. (Researcher), Matika, O. (Researcher), Paterson, T. (Researcher), Paton, B. (Researcher), Pong-Wong, R. (Researcher), Robert, C. (Researcher) & Robertson, G. (Researcher)

      Biotechnology and Biological Sciences Research Council

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    • CROATIA PROGRAMME

      Wright, A. (Principal Investigator), Adams, I. (Co-investigator), Aligianis, I. (Co-investigator), Baldock, R. (Co-investigator), Bickmore, W. (Co-investigator), Caceres, J. (Co-investigator), Dorin, J. (Co-investigator), Dunlop, M. (Co-investigator), FitzPatrick, D. (Co-investigator), Haley, C. (Co-investigator), Hastie, N. (Co-investigator), Hill, B. (Co-investigator), Jackson, I. (Co-investigator), Jackson, A. (Co-investigator), Kudla, G. (Co-investigator), Meehan, R. (Co-investigator), O'Connell, M. (Co-investigator), Overton, I. (Co-investigator), Patton, E. (Co-investigator), Taylor, M. (Co-investigator), Tenesa, A. (Co-investigator) & Van Heyningen, V. (Co-investigator)

      MRC

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