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Within\u2010dataset results were meta\u2010analyzed, followed by functional genomics analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A novel AD\u2010risk locus was identified in <jats:italic>MPDZ<\/jats:italic> on chromosome (chr) 9p23 (rs141610415, MAF\u00a0=\u00a00.002, <jats:italic>p<\/jats:italic>\u00a0=\u00a03.68\u00d710<jats:sup>\u22129<\/jats:sup>). Two additional novel common and nine rare loci were identified with suggestive associations (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a09\u00d710<jats:sup>\u22127<\/jats:sup>). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (<jats:italic>ASCL1<\/jats:italic>), suggesting that this association is modulated by regional origin of local African ancestry.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>These analyses identified novel AD\u2010associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Single variant meta\u2010analysis identified a novel genome\u2010wide significant AD\u2010risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome\u2010wide significance at <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a09\u00d710\u22127.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and\/or geographic origin of African ancestry modulates the effect at this locus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry\u2010informed genetic screening tools and therapeutic interventions.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13880","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T06:28:19Z","timestamp":1719988099000},"page":"5247-5261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Extended genome\u2010wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry"],"prefix":"10.1002","volume":"20","author":[{"given":"Nicholas R.","family":"Ray","sequence":"first","affiliation":[{"name":"Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian W.","family":"Kunkle","sequence":"additional","affiliation":[{"name":"The John P. 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