Yang, JianBakshi, AndrewZhu, ZhihongHemani, GibranVinkhuyzen, Anna A.E.Lee, Sang HongRobinson, Matthew R.Perry, John R.B.Nolte, Ilja M.van Vliet-Ostaptchouk, Jana V.Snieder, HaroldEsko, TõnuMilani, LiliMägi, ReedikMetspalu, AndresHamsten, AndersMagnusson, Patrik K.E.Pedersen, Nancy L.Ingelsson, ErikSoranzo, NicoleKeller, Matthew C.Wray, Naomi R.Goddard, Michael E.Visscher, Peter M.2016-05-022015Yang, J., A. Bakshi, Z. Zhu, G. Hemani, A. A. Vinkhuyzen, S. H. Lee, M. R. Robinson, et al. 2015. “Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index.” Nature genetics 47 (10): 1114-1120. doi:10.1038/ng.3390. http://dx.doi.org/10.1038/ng.3390.1061-4036http://nrs.harvard.edu/urn-3:HUL.InstRepos:26860080We propose a method (GREML-LDMS) to estimate heritability for human complex traits in unrelated individuals using whole-genome sequencing (WGS) data. We demonstrate using simulations based on WGS 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 ~17M imputed variants explain 56% (s.e. = 2.3%) of variance for height and 27% (s.e. = 2.5%) for body mass index (BMI), and find evidence that height- and BMI-associated variants have been under natural selection. Considering 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, missing heritability is small for both traits. For further gene discovery of complex traits, a design with SNP arrays followed by imputation is more cost-effective than WGS at current prices.en-USJournal Article2016-05-0210.1038/ng.3390