Survival of the Curviest: Noise-Driven Selection for Synergistic Epistasis.

ABSTRACT: A major goal of human genetics is to elucidate the genetic architecture of human disease, with the goal of fueling improvements in diagnosis and the understanding of disease pathogenesis. The degree to which epistasis, or non-additive effects of risk alleles at different loci, accounts for common disease traits is hotly debated, in part because the conditions under which epistasis evolves are not well understood. Using both theory and evolutionary simulation, we show that the occurrence of common diseases (i.e. unfit phenotypes with frequencies on the order of 1%) can, under the right circumstances, be expected to be driven primarily by synergistic epistatic interactions. Conditions that are necessary, collectively, for this outcome include a strongly non-linear phenotypic landscape, stron

SUBMITTER: Wilkins JF 

PROVIDER: S-EPMC4849581 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature