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We performed admixture mapping and meta\u2010analyzed the results. We then used regression analysis, adjusting for local ancestry main effects and interactions with genotype, to refine the regions identified from admixture mapping. Finally, we leveraged in silico annotation and differential gene expression data to prioritize AD\u2010related variants and genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Admixture mapping identified two genome\u2010wide significant loci on chromosomes 17p13.2 (<jats:italic>p<\/jats:italic>\u00a0=\u00a02.2\u00a0\u00d7\u00a010<jats:sup>\u22125<\/jats:sup>) and 18q21.33 (<jats:italic>p<\/jats:italic>\u00a0=\u00a01.2\u00a0\u00d7\u00a010<jats:sup>\u22125<\/jats:sup>). Our fine mapping of the chromosome 17p13.2 and 18q21.33 regions revealed several interesting genes such as the <jats:italic>MINK1<\/jats:italic>, <jats:italic>KIF1C<\/jats:italic>, and <jats:italic>BCL2<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our ancestry\u2010aware regression approach showed that AA individuals have a lower risk of AD if they inherited African ancestry admixture block at the 17p13.2 locus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>We identified two genome\u2010wide significant admixture mapping signals: on chromosomes 17p13.2 and 18q21.33, which are novel in African American (AA) populations.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our ancestry\u2010aware regression approach showed that AA individuals have a lower risk of Alzheimer's disease (AD) if they inherited African ancestry admixture block at the 17p13.2 locus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We found that the overall proportion of African ancestry does not differ between the cases and controls that suggest African genetic ancestry alone is not likely to explain the AD prevalence difference between AA and non\u2010Hispanic White populations.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.12865","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T19:29:45Z","timestamp":1671564585000},"page":"2538-2548","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Admixture mapping identifies novel Alzheimer's disease risk regions in African Americans"],"prefix":"10.1002","volume":"19","author":[{"given":"Farid","family":"Rajabli","sequence":"first","affiliation":[{"name":"John P. Hussman Institute for Human Genomics Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Tosto","sequence":"additional","affiliation":[{"name":"Gertrude H. Sergievsky Center Taub Institute for Research on the Aging Brain Departments of Neurology Psychiatry, and Epidemiology College of Physicians and Surgeons Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara L.","family":"Hamilton\u2010Nelson","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics Miller School of Medicine University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W.","family":"Kunkle","sequence":"additional","affiliation":[{"name":"John P. 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