Polygenic backgrounds influence phenotypic consequences of variants in cells, individuals, and populations.

ABSTRACT: Both rare and common genetic variants contribute to human disease, and emerging evidence suggests that they combine additively to influence disease liability. However, the non-linear relationship between disease liability and disease prevalence means that risk variants may have more severe phenotypic consequences in high-risk polygenic backgrounds and minimal impact in low-risk backgrounds, resulting in uneven selection across the population. As a result, selection coefficients may be better modeled as distributions that differ across populations, time, environments, and individuals than as single values. As the number of genes contributing to a trait and epistasis between alleles increases, so does phenotypic variance, pushing more individuals to extreme phenotypes and enhancing negative

SUBMITTER: Chapel M 

PROVIDER: S-EPMC12903375 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature