Extreme Polygenicity of Complex Traits Is Explained by Negative Selection.

ABSTRACT: Complex traits and common diseases are extremely polygenic, their heritability spread across thousands of loci. One possible explanation is that thousands of genes and loci have similarly important biological effects when mutated. However, we hypothesize that for most complex traits, relatively few genes and loci are critical, and negative selection-purging large-effect mutations in these regions-leaves behind common-variant associations in thousands of less critical regions instead. We refer to this phenomenon as flattening. To quantify its effects, we introduce a mathematical definition of polygenicity, the effective number of independently associated SNPs (M_e), which describes how evenly the heritability of a trait is spread across the genome. We developed a method, stratifie

SUBMITTER: O'Connor LJ 

PROVIDER: S-EPMC6732528 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature