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For many traits, including susceptibility to common diseases in humans,causal loci uncovered by genetic mapping studies explain only a minority of theheritable contribution to trait variation. Multiple explanations for this"missing heritability" have been proposed. Here we use a large cross betweentwo yeast strains to accurately estimate different sources of heritablevariation for 46 quantitative traits and to detect underlying loci with highstatistical power. We find that the detected loci explain nearly the entireadditive contribution to heritable variation for the traits studied. We alsoshow that the contribution to heritability of gene-gene interactions variesamong traits, from near zero to 50%. Detected two-locus interactions explainonly a minority of this contribution. These results substantially advance ourunderstanding of the missing heritability problem and have importantimplications for future studies of complex and quantitative traits.

Finding the sources of missing heritability in a yeast cross