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However, the prevalence of different modes of selection on genomic regions associated with variation in traits remains poorly understood. To address this, we developed an efficient computational framework to calculate positive and negative enrichment of different evolutionary measures among regions associated with complex traits. We applied the framework to summary statistics from &gt;900 genome-wide association studies (GWASs) and 11 evolutionary measures of sequence constraint, population differentiation, and allele age while accounting for linkage disequilibrium, allele frequency, and other potential confounders. We demonstrate that this framework yields consistent results across GWASs with variable sample sizes, numbers of trait-associated SNPs, and analytical approaches. The resulting evolutionary atlas maps diverse signatures of selection on genomic regions associated with complex human traits on an unprecedented scale. We detected positive enrichment for sequence conservation among trait-associated regions for the majority of traits (&gt;77% of 290 high power GWASs), which included reproductive traits. Many traits also exhibited substantial positive enrichment for population differentiation, especially among hair, skin, and pigmentation traits. In contrast, we detected widespread negative enrichment for signatures of balancing selection (51% of GWASs) and absence of enrichment for evolutionary signals in regions associated with late-onset Alzheimer\u2019s disease. These results support a pervasive role for negative selection on regions of the human genome that contribute to variation in complex traits, but also demonstrate that diverse modes of evolution are likely to have shaped trait-associated loci. This atlas of evolutionary signatures across the diversity of available GWASs will enable exploration of the relationship between the genetic architecture and evolutionary processes in the human genome.<\/jats:p>","DOI":"10.1371\/journal.pgen.1010494","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T13:38:18Z","timestamp":1667828298000},"page":"e1010494","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mosaic patterns of selection in genomic regions associated with diverse human traits"],"prefix":"10.1371","volume":"18","author":[{"given":"Abin","family":"Abraham","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0068-6703","authenticated-orcid":true,"given":"Abigail L.","family":"LaBella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John A.","family":"Capra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7248-6551","authenticated-orcid":true,"given":"Antonis","family":"Rokas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,11,7]]},"reference":[{"issue":"5","key":"pgen.1010494.ref001","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/s41576-020-00305-9","article-title":"The influence of evolutionary history on human health and disease","volume":"22","author":"ML Benton","year":"2021","journal-title":"Nature Reviews Genetics"},{"issue":"4","key":"pgen.1010494.ref002","doi-asserted-by":"crossref","first-page":"R208","DOI":"10.1016\/j.cub.2009.11.055","article-title":"The Genetics of Human Adaptation: Hard Sweeps, Soft Sweeps, and Polygenic Adaptation","volume":"20","author":"JK Pritchard","year":"2010","journal-title":"Current Biology"},{"issue":"6308","key":"pgen.1010494.ref003","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.aaf5098","article-title":"Going global by adapting local: A review of recent human adaptation","volume":"354","author":"S Fan","year":"2016","journal-title":"Science"},{"issue":"6","key":"pgen.1010494.ref004","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/nrg3936","article-title":"Evidence for archaic adaptive introgression in humans","volume":"16","author":"F Racimo","year":"2015","journal-title":"Nature reviews Genetics"},{"issue":"7637","key":"pgen.1010494.ref005","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nature21347","article-title":"Tracing the peopling of the world through genomics","volume":"541","author":"R Nielsen","year":"2017","journal-title":"Nature"},{"issue":"1","key":"pgen.1010494.ref006","first-page":"1","article-title":"On the Evolution of Lactase Persistence in Humans","volume":"18","author":"L S\u00e9gurel","year":"2016","journal-title":"Annual Review of Genomics and Human Genetics"},{"issue":"7583","key":"pgen.1010494.ref007","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature16152","article-title":"Genome-wide patterns of selection in 230 ancient Eurasians","volume":"528","author":"I Mathieson","year":"2015","journal-title":"Nature"},{"issue":"6","key":"pgen.1010494.ref008","doi-asserted-by":"crossref","first-page":"e3000742","DOI":"10.1371\/journal.pbio.3000742","article-title":"Why and when was lactase persistence selected for? 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