Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index

Nat Genet. 2015 Oct;47(10):1114-20. doi: 10.1038/ng.3390. Epub 2015 Aug 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Height / genetics*
  • Body Mass Index*
  • Genetic Variation*
  • Genome, Human
  • Humans

Associated data

  • dbGaP/PHS000090
  • dbGaP/PHS000091
  • dbGaP/PHS000428