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

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 12 complex human diseases using family history of disease in 1,555,906 individuals of white ancestry from the UK Biobank. Estimates using simple family-based statistical models were inflated on average by 47% when compared with those from structural equation modeling (SEM), which specifically accounted for shared familial environmental factors. In addition, heritabilities estimated using SNP data explained an average of 44.2% of the simple family-based estimates across diseases and an average of 57.3% of the SEM-estimated heritabilities, accounting 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.

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Figure 1: Heritability estimates using SEM family-based models and SNPs.

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Acknowledgements

We thank I. White for his helpful comments. This research has been conducted using the UK Biobank resource and funded by the Roslin Institute Strategic Programme Grant from the BBSRC (BB/J004235/1). C.S.H. and A.T. also acknowledge funding from the MRC. SNP heritability estimates were calculated using the ARCHER UK National Supercomputing Service.

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Authors and Affiliations

Authors

Contributions

A.T. and C.S.H. conceived and designed the study. M.M. and A.T. performed the statistical analysis. O.C.-X. and K.R. carried out the SNP filtering and quality control. M.M., C.S.H. and A.T. wrote the manuscript. R.P.-W. performed the simulations and contributed ideas and quantitative genetics expertise. All authors read and approved the manuscript.

Corresponding author

Correspondence to Albert Tenesa.

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The authors declare no competing financial interests.

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Supplementary Figures 1 and 2, Supplementary Tables 1–16 and Supplementary Note. (PDF 665 kb)

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Muñoz, M., Pong-Wong, R., Canela-Xandri, O. et al. Evaluating the contribution of genetics and familial shared environment to common disease using the UK Biobank. Nat Genet 48, 980–983 (2016). https://doi.org/10.1038/ng.3618

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