Evidence for Weak Selective Constraint on Human Gene Expression.

ABSTRACT: Gene expression variation is a major contributor to phenotypic variation in human complex traits. Selection on complex traits may therefore be reflected in constraint on gene expression. Here, we explore the effects of stabilizing selection on cis-regulatory genetic variation in humans. We analyze patterns of expression variation at copy number variants and find evidence for selection against large increases in gene expression. Using allele-specific expression (ASE) data, we further show evidence of selection against smaller-effect variants. We estimate that, across all genes, singletons in a sample of 122 individuals have ∼2.2× greater effects on expression variation than the average variant across allele frequencies. Despite their increased effect size relative to common variants, we est

SUBMITTER: Glassberg EC 

PROVIDER: S-EPMC6366908 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature