“Genetic Variance Estimation With Imputed Variants Finds Negligible Missing Heritability for Human Height and Body Mass Index”, 2015-08-31 (; backlinks; similar):
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-associated 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.