Finding the sources of missing heritability in a yeast cross

TL;DR

This study uses a large yeast cross to quantify sources of heritable variation, revealing that detected loci account for nearly all additive heritability and that gene-gene interactions vary widely among traits.

Contribution

It provides a comprehensive analysis of heritability sources in yeast, demonstrating that most additive heritability can be explained by detected loci and highlighting the variable role of gene interactions.

Findings

Detected loci explain nearly all additive heritability.

Gene-gene interaction contributions vary from near zero to 50%.

Two-locus interactions account for a minority of heritability.

Abstract

For many traits, including susceptibility to common diseases in humans, causal loci uncovered by genetic mapping studies explain only a minority of the heritable contribution to trait variation. Multiple explanations for this "missing heritability" have been proposed. Here we use a large cross between two yeast strains to accurately estimate different sources of heritable variation for 46 quantitative traits and to detect underlying loci with high statistical power. We find that the detected loci explain nearly the entire additive contribution to heritable variation for the traits studied. We also show that the contribution to heritability of gene-gene interactions varies among traits, from near zero to 50%. Detected two-locus interactions explain only a minority of this contribution. These results substantially advance our understanding of the missing heritability problem and have important implications for future studies of complex and quantitative traits.