Weak Epistasis Generally Stabilizes Phenotypes in a Mouse Intercross

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Abstract

<title>Author Summary</title> <p>The role of statistical epistasis in the genetic architecture of complex traits has been of great interest to the genetics community since Fisher introduced the concept in 1918. However, assessing epistasis in human and model organism populations has been impeded by limited statistical power. To mitigate this limitation, we analyzed bone and body composition traits in an unusually large mouse intercross population of over 2000 mice, paired with a recently-developed computational approach that leverages information to detect interactions across multiple phenotypes. We discovered a large network of highly significant genetic interactions between variants that influence complex body composition traits. Although epistasis was abundant, the interaction network was dominated by epistasis that stabilizes phenotypes by reducing phenotypic deviation from the parent strains. Nevertheless, the observed network provides an overview of genetic architecture and specific hypotheses of how QTL combine to affect phenotypes. These findings suggest that epistatic effects are generally of lesser magnitude than main QTL effects, and therefore are unlikely to account for major components of variance, but also reinforce genetic interaction analysis as a potent tool for dissecting the biology of complex traits.</p>

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Tyler, A. L., Donahue, L. R., Churchill, G. A., & Carter, G. W. (2016). Weak Epistasis Generally Stabilizes Phenotypes in a Mouse Intercross. PLoS Genetics, 12(2). https://doi.org/10.1371/journal.pgen.1005805

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