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However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the\n                    <jats:italic>APOE4<\/jats:italic>\n                    allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (\n                    <jats:italic>N<\/jats:italic>\n                    = 1266, 50% female),\n                    <jats:italic>APOE4<\/jats:italic>\n                    is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further,\n                    <jats:italic>APOE4<\/jats:italic>\n                    carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between\n                    <jats:italic>APOE4<\/jats:italic>\n                    and lipids may be beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.\n                  <\/jats:p>","DOI":"10.7554\/elife.68231","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T06:15:59Z","timestamp":1632896159000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.68231","source":"Crossref","is-referenced-by-count":57,"title":["APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6685-5533","authenticated-orcid":true,"given":"Angela R","family":"Garcia","sequence":"first","affiliation":[{"name":"Center for Evolution and Medicine, Arizona State University","place":["Tempe, United States"]},{"name":"Department of Anthropology, Emory University","place":["Atlanta, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7617-3958","authenticated-orcid":true,"given":"Caleb","family":"Finch","sequence":"additional","affiliation":[{"name":"Leonard Davis School of Gerontology, Dornsife College, University of Southern California, Los Angeles","place":["Los Angeles, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1071-9970","authenticated-orcid":true,"given":"Margaret","family":"Gatz","sequence":"additional","affiliation":[{"name":"Center for Economic and Social Research, University of Southern California, Los Angeles","place":["Los Angeles, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kraft","sequence":"additional","affiliation":[{"name":"Department of Anthropology, University of California, Santa Barbara","place":["Santa Barbara, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Eid Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Medicine, Universidad de San Sim\u00f3n","place":["Cochabamba, Bolivia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Cummings","sequence":"additional","affiliation":[{"name":"Institute for Economics and Society, Chapman University","place":["Orange, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Charifson","sequence":"additional","affiliation":[{"name":"Vilcek Institute of Graduate Biomedical Sciences, New York University","place":["New York, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Buetow","sequence":"additional","affiliation":[{"name":"Center for Evolution and Medicine, Arizona State University","place":["Tempe, United States"]},{"name":"School of Life Sciences, Arizona State University","place":["Tempe, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bret A","family":"Beheim","sequence":"additional","affiliation":[{"name":"Department of Human Behavior, Ecology and Culture, Max Planck Institute for Evolutionary Anthropology","place":["Leipzig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2384-5239","authenticated-orcid":true,"given":"Hooman","family":"Allayee","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine and Biochemistry & Molecular Medicine, Keck School of Medicine, University of Southern California, Irvine","place":["Irvine, United States"]},{"name":"Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Irvine","place":["Irvine, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S","family":"Thomas","sequence":"additional","affiliation":[{"name":"Long Beach Memorial, Long Beach and University of California Irvine","place":["Irvine, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5985-9643","authenticated-orcid":true,"given":"Jonathan","family":"Stieglitz","sequence":"additional","affiliation":[{"name":"Institute for Advanced Study in Toulouse, Universite Toulouse","place":["Toulouse, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5661-527X","authenticated-orcid":true,"given":"Michael D","family":"Gurven","sequence":"additional","affiliation":[{"name":"Department of Anthropology, University of California, Santa Barbara","place":["Santa Barbara, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillard","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Institute for Economics and Society, Chapman 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