Analysis of genetic dominance in the UK Biobank

Classical statistical genetics theory defines dominance as any deviation from a purely additive, or dosage, effect of a genotype on a trait, which is known as the dominance deviation. Dominance is well documented in plant and animal breeding. Outside of rare monogenic traits, however, evidence in humans is limited. We systematically examined common genetic variation across 1060 traits in a large population cohort (UK Biobank, N = 361,194 samples analyzed) for evidence of dominance effects. We then developed a computationally efficient method to rapidly assess the aggregate contribution of dominance deviations to heritability. Lastly, observing that dominance associations are inherently less correlated between sites at a genomic locus than their additive counterparts, we explored whether they may be leveraged to identify causal variants more confidently.

Automated summary

Classical statistical genetics theory defines dominance as any deviation from a purely additive effect of a genotype on a trait. Dominance is well documented in plant and animal breeding, but limited evidence exists in humans outside of rare monogenic traits. This study systematically examined common genetic variation in a large population cohort for evidence of dominance effects across 1060 traits. The researchers developed a computationally efficient method to assess the aggregate contribution of dominance deviations to heritability and explored the potential of leveraging dominance associations to identify causal variants.