Extreme Polygenicity of Complex Traits Is Explained by Negative Selection

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.

Source: The American Journal of Human Genetics - August 7, 2019 Category: Genetics & Stem Cells Authors: Luke J. O'Connor, Armin P. Schoech, Farhad Hormozdiari, Steven Gazal, Nick Patterson, Alkes L. Price Tags: Article Source Type: research