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Association of AD with 253,421 bi-allelic variants with minor allele count\u2009\u2265\u200920 in the total sample and each population group was evaluated using GENESIS. Gene-based tests comprising predicted moderate and high-impact variants were performed using SAIGE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Novel study-wide significant associations (p\u2009&lt;\u20091.97\u2009\u00d7\u200910\n                      <jats:sup>\u22127<\/jats:sup>\n                      ) were identified with variants enriched among the Amish in\n                      <jats:italic toggle=\"yes\">BTBD8<\/jats:italic>\n                      (rs927193859, p\u2009=\u20091.58 x10\n                      <jats:sup>\u221210<\/jats:sup>\n                      ),\n                      <jats:italic toggle=\"yes\">LINGO1<\/jats:italic>\n                      (rs150289554, p\u2009=\u20098.60\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ), and\n                      <jats:italic toggle=\"yes\">KCNG2<\/jats:italic>\n                      (rs140218057, p\u2009=\u20091.77\u2009\u00d7\u200910\n                      <jats:sup>\u22127<\/jats:sup>\n                      ) in the total sample. Population-specific analyses confirmed significant associations with\n                      <jats:italic toggle=\"yes\">APOE<\/jats:italic>\n                      in all groups and detected an association in CH individuals with the\n                      <jats:italic toggle=\"yes\">PSEN1<\/jats:italic>\n                      missense mutation G206A (p\u2009=\u20093.07\u2009\u00d7\u200910\n                      <jats:sup>\u22127<\/jats:sup>\n                      ), a variant that was previously linked to early-onset AD in Hispanics. Gene-based tests highlighted significant associations with\n                      <jats:italic toggle=\"yes\">LINGO1<\/jats:italic>\n                      (p\u2009=\u20092.75\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      ),\n                      <jats:italic toggle=\"yes\">DYNLT4<\/jats:italic>\n                      (p\u2009=\u20092.80\u2009\u00d7\u200910\n                      <jats:sup>\u22127<\/jats:sup>\n                      ), and\n                      <jats:italic toggle=\"yes\">ADCY4<\/jats:italic>\n                      (p\u2009=\u20097.43\u2009\u00d7\u200910\n                      <jats:sup>\u22127<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified rare variants in novel genes which provide new insights into AD pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251405497","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T17:27:05Z","timestamp":1766424425000},"page":"1274-1286","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-ancestry exome-wide study identifies variants associated with Alzheimer's disease protection"],"prefix":"10.1177","volume":"109","author":[{"given":"Zainab","family":"Khurshid","sequence":"first","affiliation":[{"name":"Bioinformatics Program, Boston University, Boston, MA, USA"},{"name":"Department of Medicine (Biomedical Genetics), Boston University Chobanian &amp; 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