Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index.
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Abstract | We propose a method (GREML-LDMS) to estimate heritability for human complex traits in unrelated individuals using whole-genome sequencing data. We demonstrate using simulations based on whole-genome sequencing data that ∼97% and ∼68% of variation at common and rare variants, respectively, can be captured by imputation. Using the GREML-LDMS method, we estimate from 44,126 unrelated individuals that all ∼17 million imputed variants explain 56% (standard error (s.e.) = 2.3%) of variance for height and 27% (s.e. = 2.5%) of variance for body mass index (BMI), and we find evidence that height- and BMI-associated variants have been under natural selection. Considering the imperfect tagging of imputation and potential overestimation of heritability from previous family-based studies, heritability is likely to be 60-70% for height and 30-40% for BMI. Therefore, the missing heritability is small for both traits. For further discovery of genes associated with complex traits, a study design with SNP arrays followed by imputation is more cost-effective than whole-genome sequencing at current prices. |
Year of Publication | 2015
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Journal | Nat Genet
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Volume | 47
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Issue | 10
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Pages | 1114-20
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Date Published | 2015 Oct
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ISSN | 1546-1718
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URL | |
DOI | 10.1038/ng.3390
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PubMed ID | 26323059
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PubMed Central ID | PMC4589513
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Grant list | R01MH100141 / MH / NIMH NIH HHS / United States
102215 / Wellcome Trust / United Kingdom
MC_UU_12015/2 / Medical Research Council / United Kingdom
MC_PC_15018 / Medical Research Council / United Kingdom
MC_U106179472 / Medical Research Council / United Kingdom
R01 MH100141 / MH / NIMH NIH HHS / United States
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