Quantifying the contribution of dominance effects to complex trait variation in biobank-scale data

Abstract

The proportion of variation in complex traits that can be attributed to non-additive genetic effects has been a topic of intense debate. The availability of Biobank-scale datasets of genotype and trait data from unrelated individuals opens up the possibility of obtaining precise estimates of the contribution of non-additive genetic effects. We present an efficient method that can partition the variation in complex traits into variance that can be attributed to additive (additive heritability) and dominance (dominance heritability) effects across all genotyped SNPs in a large collection of unrelated individuals. Over a wide range of genetic architectures, our method yields unbiased estimates of heritability. We applied our method, in turn, to array genotypes as well as imputed genotypes (at common SNPs with minor allele frequency, MAF > 1%) and 50 quantitative traits measured in 291, 273 unrelated white British individuals in the UK Biobank. Averaged across these 50 traits, we find that additive heritability on array SNPs is 21.86% while dominance heritability is 0.13% (about 0.48% of the additive heritability) with qualitatively similar results for imputed genotypes. We find no evidence for dominance heritability ([Formula] accounting for the number of traits tested) and estimate that dominance heritability is unlikely to exceed 1% for the traits analyzed. Our analyses indicate a limited contribution of dominance heritability to complex trait variation.