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Nat Commun. 2015 Nov 5;6:8712. doi: 10.1038/ncomms9712.

Genetic interactions contribute less than additive effects to quantitative trait variation in yeast.

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Department of Human Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA.
Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, California 90095, USA.
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08540, USA.
Twist Bioscience, San Francisco, California 94158, USA.
Department of Biological Chemistry, University of California, Los Angeles, California 90095, USA.


Genetic mapping studies of quantitative traits typically focus on detecting loci that contribute additively to trait variation. Genetic interactions are often proposed as a contributing factor to trait variation, but the relative contribution of interactions to trait variation is a subject of debate. Here we use a very large cross between two yeast strains to accurately estimate the fraction of phenotypic variance due to pairwise QTL-QTL interactions for 20 quantitative traits. We find that this fraction is 9% on average, substantially less than the contribution of additive QTL (43%). Statistically significant QTL-QTL pairs typically have small individual effect sizes, but collectively explain 40% of the pairwise interaction variance. We show that pairwise interaction variance is largely explained by pairs of loci at least one of which has a significant additive effect. These results refine our understanding of the genetic architecture of quantitative traits and help guide future mapping studies.

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