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Laboratory yeast crosses reveal limited epistasis in the genetic basis of complex traits

Gupta, M.; Holmes, C. M.; Belousova, J.; Gopalakrishnan, S.; Rego-Costa, A.; Desai, M. M.

2026-04-06 genetics
10.64898/2026.04.04.716439 bioRxiv
Show abstract

Mapping the genetic basis of complex traits is complicated by the presence of epistatic interactions between loci. While work in molecular genetics identifies numerous specific genetic interactions, statistical analyses of quantitative traits frequently conclude that additive (nonepistatic) models explain most heritable variation. However, these conclusions are typically limited by the narrow range of genetic relatedness(e.g. in F1 offspring of a biparental or circular cross). Here, we use a barcoded panel of Saccharomyces cerevisiae genotypes with a broad range of relatedness to quantify the effects of epistasis on the genetic architecture of seven complex traits. We find limited contributions of epistasis to the genetic basis of these traits. These results indicate that epistasis beyond that detected in standard yeast crosses may exist, yet it contributes little to phenotypic variance in these systems.

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