TY - JOUR T1 - An evolutionary compass for elucidating selection mechanisms shaping complex traits JF - bioRxiv DO - 10.1101/173815 SP - 173815 AU - Lawrence H. Uricchio AU - Hugo C. Kitano AU - Alexander Gusev AU - Noah A. Zaitlen Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/06/07/173815.abstract N2 - Polygenic selection is likely to target some human traits, but the specific evolutionary mechanisms driving complex trait variation are largely unknown. We developed an evolutionary compass for detecting selection and mutational bias that uses polarized GWAS summary statistics from a single population. We found evidence for selection and mutational bias acting on variation in five traits (BMI, schizophrenia, Crohn’s disease, educational attainment, and height). We then used model-based analyses to show that these signals can be explained by stabilizing selection with shifts in the fitness-phenotype relationship. We additionally provide evidence that selection has acted on Neanderthal alleles for height, schizophrenia, and depression, and discuss potential sources of confounding. Our results provide a flexible and powerful framework for evolutionary analysis of complex phenotypes in humans and other organisms, and provide insights into the evolutionary mechanisms driving variation in human polygenic traits. ER -