PT - JOURNAL ARTICLE AU - Mashaal Sohail TI - Investigating relative contributions to psychiatric disease architecture from sequence elements originating across multiple evolutionary time-scales AID - 10.1101/2022.02.28.482389 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.02.28.482389 4099 - http://biorxiv.org/content/early/2022/03/01/2022.02.28.482389.short 4100 - http://biorxiv.org/content/early/2022/03/01/2022.02.28.482389.full AB - It remains an open question when and why psychiatric and other disease evolved in human evolutionary history. We harness large genome-wide association studies and recent studies that have identified human-gained epigenetic marks, selective sweeps, archaic introgression, and accelerated evolution to help tackle this question by assessing the enrichment of heritability in these sequence elements for 41 complex traits. We find that human-gained epigenetic elements in the fetal brain harbor variants affecting skeletal, dermatological, and respiratory traits early and psychiatric traits later in development, that genomic sequences under selection since our divergence with Neanderthals are enriched in heritability for autism, and that regions depleted in ancestry from other hominids contribute more to heritability for psychiatric than other traits. Psychiatric disease may be a concomitant outcome of the evolutionary processes that made us uniquely human.One-Sentence Summary Variants that cause autism and other psychiatric disease today co-locate with sequence elements that have been important during human evolution.Competing Interest StatementThe authors have declared no competing interest.