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Unbiased associations between 6881 metabolites and 332,772 common genetic variants were tested, adjusted for age, sex, and both metabolomic and genomic principal components.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      We identified 72 SNP\u2010metabolite associations spanning 66 genes and 12 metabolite classes, including\n                      <jats:italic>PYROXD2<\/jats:italic>\n                      \/N6\u2010methyllysine,\n                      <jats:italic>FAAH<\/jats:italic>\n                      \/myristoylglycine, and\n                      <jats:italic>FADS2<\/jats:italic>\n                      \/arachidonic acid. Additionally, we found differences in genetic regulation of metabolites among individuals with clinically\u2010defined AD compared to biomarker\u2010defined AD based on a published plasma P\u2010tau181 cutoff. We also found more SNP\u2010metabolite associations among males compared to females.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>In summary, we identified sex\u2010 and disease\u2010specific genetic regulators of plasma metabolites, revealing unique biological mechanisms of genetic perturbations in AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Genetic regulators of the metabolome spanned 66 genes and 12 metabolite classes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Clinically versus biomarker\u2010defined Alzheimer's disease (AD) affects genetic regulators of the metabolome.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Most metabolite quantitative trait loci (QTLs) are not shared between males and females.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70898","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T16:23:03Z","timestamp":1763137383000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic regulation of the metabolome differs by sex, Alzheimer's disease stage, and plasma biomarker status"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6439-3999","authenticated-orcid":false,"given":"Jaclyn M.","family":"Eissman","sequence":"first","affiliation":[{"name":"The Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"},{"name":"Gertrude H. Sergievsky Center Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Qiao","sequence":"additional","affiliation":[{"name":"The Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"},{"name":"Gertrude H. Sergievsky Center Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vrinda","family":"Kalia","sequence":"additional","affiliation":[{"name":"Mailman School of Public Health Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielba","family":"Zerlin\u2010Esteves","sequence":"additional","affiliation":[{"name":"Gertrude H. Sergievsky Center Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolly","family":"Reyes\u2010Dumeyer","sequence":"additional","affiliation":[{"name":"The Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"},{"name":"Gertrude H. Sergievsky Center Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Piriz","sequence":"additional","affiliation":[{"name":"The Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"},{"name":"Gertrude H. Sergievsky Center Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurabh","family":"Dubey","sequence":"additional","affiliation":[{"name":"Mailman School of Public Health Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"Mailman School of Public Health Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie J.","family":"Lee","sequence":"additional","affiliation":[{"name":"The Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"},{"name":"Gertrude H. Sergievsky Center Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael A.","family":"Lantigua","sequence":"additional","affiliation":[{"name":"Vagelos College of Physicians and Surgeons Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Medrano","sequence":"additional","affiliation":[{"name":"Pontificia Universidad Cat\u00f3lica Madre y Maestra  Santiago Rep\u00fablica Dominicana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diones Rivera","family":"Mejia","sequence":"additional","affiliation":[{"name":"CEDIMAT, Plaza de la Salud, Dr. Juan Manuel Taveras Rodr\u00edguez C\/Pepillo Salcedo esq. 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