An evolutionary compass for detecting signals of polygenic selection and mutational bias. Issue 1 (25th January 2019)

• Record Type: Journal Article
• Authors: Uricchio, Lawrence H.; Kitano, Hugo C.; Gusev, Alexander; Zaitlen, Noah A.
• Is Part Of: Evolution letters. Volume 3:Issue 1(2019)
• Page Start: 69
• Page End: 79
• Publication Date: 2019-01-25
• Subjects: Complex traits -- mutation bias -- natural selection -- polygenic selection; Evolution (Biology) -- Periodicals; Evolution (Biology); Biological Evolution; Electronic journals; Fulltext; Internet Resources; Periodicals; Periodicals; Periodical; 576.8
• DOI: 10.1002/evl3.97
• Languages: English
• ISSNs: 2056-3744

Abstract

Abstract: Selection and mutation shape the genetic variation underlying human traits, but the specific evolutionary mechanisms driving complex trait variation are largely unknown. We developed a statistical method that uses polarized genome‐wide association study (GWAS) summary statistics from a single population to detect signals of mutational bias and selection. We found evidence for nonneutral signals on variation underlying several traits (body mass index [BMI], schizophrenia, Crohn's disease, educational attainment, and height). We then used simulations that incorporate simultaneous negative and positive selection to show that these signals are consistent with mutational bias and shifts in the fitness‐phenotype relationship, but not stabilizing selection or mutational bias alone. We additionally replicate two of our top three signals (BMI and educational attainment) in an external cohort, and show that population stratification may have confounded GWAS summary statistics for height in the GIANT cohort. Our results provide a flexible and powerful framework for evolutionary analysis of complex phenotypes in humans and other species, and offer insights into the evolutionary mechanisms driving variation in human polygenic traits.