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Recently, large-scale genome-wide association studies (GWAS) on immunological traits have underscored the notion that genetic predisposition to infectious diseases likely stems from the contribution of several thousand loci across the human genome. To model the polygenic inheritance of these traits, multiple variants can be combined into polygenic risk scores (PRS), which estimate an individual\u2019s genetic predisposition for a trait. By combining present-day GWAS statistics from large European biobanks with genomic data from more than 3,500 ancient individuals from Western Eurasia, we characterize temporal changes in four highly heritable infectious disease-related traits over a span of 10,000 years. In doing so, we account for variation in these traits across time, space, and genetic ancestries, and demonstrate that the observed patterns cannot be explained by genetic drift alone. Our findings suggest that major disease outbreaks in human history are associated with shifts in polygenic traits in human populations. Specifically, three events \u2013 the Justinian Plague, Antonine Plague, and early medieval measles outbreaks \u2013 coincide with significant shifts in the polygenic profiles of these traits. Using a Gene Ontology enrichment approach, we show that these shifts involve multiple systemic biological processes, with a consistent emphasis on metabolic pathways modulating immunological responses both directly and indirectly.<\/jats:p>","DOI":"10.64898\/2026.04.07.717059","type":"posted-content","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T05:30:18Z","timestamp":1775712618000},"source":"Crossref","is-referenced-by-count":0,"title":["Temporal shifts in polygenic traits track major epidemics in Western Eurasia"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4747-2385","authenticated-orcid":false,"given":"Flavio","family":"De Angelis","sequence":"first","affiliation":[{"name":"School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, 85281, U.S.A"},{"name":"Institute of Human Origins, Arizona State University, Tempe, AZ, 85287, U.S.A"},{"name":"Department of Mental and Physical Health, and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Naples, 80138, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-1114","authenticated-orcid":false,"given":"Lars","family":"Fehren-Schmitz","sequence":"additional","affiliation":[{"name":"Department of Mental and Physical Health, and Preventive Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Naples, 80138, Italy"},{"name":"UCSC Paleogenomics, Department of Anthropology, University of California Santa Cruz, Santa Cruz, CA, 95064, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8827-238X","authenticated-orcid":false,"given":"Carlos Eduardo G.","family":"Amorim","sequence":"additional","affiliation":[{"name":"School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, 85281, U.S.A"},{"name":"Institute of Human Origins, Arizona State University, Tempe, AZ, 85287, U.S.A"},{"name":"Center for Evolution and Medicine, Arizona State University, Tempe, AZ, 85281, U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041019201308000_2026.04.07.717059v1.1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mst080"},{"key":"2026041019201308000_2026.04.07.717059v1.2","doi-asserted-by":"publisher","DOI":"10.1111\/eva.12586"},{"key":"2026041019201308000_2026.04.07.717059v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-00305-9"},{"key":"2026041019201308000_2026.04.07.717059v1.4","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2022.0002"},{"key":"2026041019201308000_2026.04.07.717059v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06618-z"},{"key":"2026041019201308000_2026.04.07.717059v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06705-1"},{"key":"2026041019201308000_2026.04.07.717059v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.xgen.2022.100248"},{"key":"2026041019201308000_2026.04.07.717059v1.8","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-022-08888-9"},{"key":"2026041019201308000_2026.04.07.717059v1.9","doi-asserted-by":"publisher","DOI":"10.13110\/humanbiology.89.1.03"},{"key":"2026041019201308000_2026.04.07.717059v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05349-x"},{"key":"2026041019201308000_2026.04.07.717059v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2698"},{"key":"2026041019201308000_2026.04.07.717059v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34461-9"},{"key":"2026041019201308000_2026.04.07.717059v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-020-00297-6"},{"key":"2026041019201308000_2026.04.07.717059v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2017.09.028"},{"key":"2026041019201308000_2026.04.07.717059v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.06.005"},{"key":"2026041019201308000_2026.04.07.717059v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41439-022-00226-5"},{"key":"2026041019201308000_2026.04.07.717059v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00257-5"},{"key":"2026041019201308000_2026.04.07.717059v1.18","doi-asserted-by":"crossref","unstructured":"Butkovi\u0107, A. , and Elena, S.F . 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