Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index
2015 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, no 10, 1114-1120 p.Article in journal (Refereed) Published
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 similar to 97% and similar to 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 similar to 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.
Place, publisher, year, edition, pages
2015. Vol. 47, no 10, 1114-1120 p.
IdentifiersURN: urn:nbn:se:uu:diva-265693DOI: 10.1038/ng.3390ISI: 000361969900006PubMedID: 26323059OAI: oai:DiVA.org:uu-265693DiVA: diva2:866946
FunderNIH (National Institute of Health), R01MH100141