missing heritability

Brown AA, Buil A, Viñuela A, Lappalainen T, Zheng HF, Richards JB, Small KS, Spector TD, Dermitzakis ET, Durbin R 2014 Genetic interactions affecting human gene expression identified by variance association mapping. eLife 3:e01381.

• non-additive interaction between genetic variants, or epistasis, is a possible explanation for the gap between heritability of complex traits and the variation explained by identified genetic loci
• interactions give rise to genotype dependent variance
• the identification of variance quantitative trait loci can be an intermediate step to discover both epistasis and gene by environment effects
• we identify a candidate set of 508 variance associated SNPs
• GxE plays a role in ~70% of these associations
• further investigation of these loci reveals 57 epistatic interactions that replicated in a smaller dataset, explaining on average 4.3% of phenotypic variance
• in 24 cases, more variance is explained by the interaction than their additive contributions