000271868 001__ 271868 000271868 005__ 20250202000613.0 000271868 0247_ $$2pmc$$apmc:PMC11350055 000271868 0247_ $$2doi$$a10.1002/alz.13880 000271868 0247_ $$2pmid$$apmid:38958117 000271868 0247_ $$2ISSN$$a1552-5260 000271868 0247_ $$2ISSN$$a1552-5279 000271868 0247_ $$2altmetric$$aaltmetric:173643513 000271868 037__ $$aDZNE-2024-01080 000271868 041__ $$aEnglish 000271868 082__ $$a610 000271868 1001_ $$aRay, Nicholas R$$b0 000271868 245__ $$aExtended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry. 000271868 260__ $$aHoboken, NJ$$bWiley$$c2024 000271868 3367_ $$2DRIVER$$aarticle 000271868 3367_ $$2DataCite$$aOutput Types/Journal article 000271868 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1725444108_32477 000271868 3367_ $$2BibTeX$$aARTICLE 000271868 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000271868 3367_ $$00$$2EndNote$$aJournal Article 000271868 520__ $$aDespite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts.Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses.A novel AD-risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, p = 3.68×10-9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9×10-7). 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 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry.These analyses identified novel AD-associated 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.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. 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. Single variant meta-analysis identified a novel genome-wide significant AD-risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome-wide significance at p < 9×10-7. 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. 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-informed genetic screening tools and therapeutic interventions. 000271868 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000271868 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000271868 650_7 $$2Other$$aAfrican Americans 000271868 650_7 $$2Other$$aAfrican genome Panel 000271868 650_7 $$2Other$$aAlzheimer's disease 000271868 650_7 $$2Other$$agenome‐wide association study 000271868 650_2 $$2MeSH$$aHumans 000271868 650_2 $$2MeSH$$aAlzheimer Disease: genetics 000271868 650_2 $$2MeSH$$aAlzheimer Disease: ethnology 000271868 650_2 $$2MeSH$$aGenome-Wide Association Study 000271868 650_2 $$2MeSH$$aGenetic Predisposition to Disease: genetics 000271868 650_2 $$2MeSH$$aBlack People: genetics 000271868 650_2 $$2MeSH$$aLinkage Disequilibrium 000271868 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide: genetics 000271868 650_2 $$2MeSH$$aFemale 000271868 650_2 $$2MeSH$$aMale 000271868 650_2 $$2MeSH$$aAged 000271868 7001_ $$aKunkle, Brian W$$b1 000271868 7001_ $$aHamilton-Nelson, Kara$$b2 000271868 7001_ $$aKurup, Jiji T$$b3 000271868 7001_ $$aRajabli, Farid$$b4 000271868 7001_ $$aQiao, Min$$b5 000271868 7001_ $$aVardarajan, Badri N$$b6 000271868 7001_ $$0P:(DE-2719)2811286$$aCosacak, Mehmet I$$b7$$udzne 000271868 7001_ $$0P:(DE-2719)2811030$$aKizil, Caghan$$b8$$udzne 000271868 7001_ $$aJean-Francois, Melissa$$b9 000271868 7001_ $$aCuccaro, Michael$$b10 000271868 7001_ $$aReyes-Dumeyer, Dolly$$b11 000271868 7001_ $$aCantwell, Laura$$b12 000271868 7001_ $$aKuzma, Amanda$$b13 000271868 7001_ $$aVance, Jeffery M$$b14 000271868 7001_ $$aGao, Sujuan$$b15 000271868 7001_ $$aHendrie, Hugh C$$b16 000271868 7001_ $$aBaiyewu, Olusegun$$b17 000271868 7001_ $$aOgunniyi, Adesola$$b18 000271868 7001_ $$aAkinyemi, Rufus O$$b19 000271868 7001_ $$aConsortium, Alzheimer's Disease Genetics$$b20$$eCollaboration Author 000271868 7001_ $$aLee, Wan-Ping$$b21 000271868 7001_ $$aMartin, Eden R$$b22 000271868 7001_ $$aWang, Li-San$$b23 000271868 7001_ $$aBeecham, Gary W$$b24 000271868 7001_ $$aBush, William S$$b25 000271868 7001_ $$aXu, Wanying$$b26 000271868 7001_ $$aJin, Fulai$$b27 000271868 7001_ $$aWang, Liyong$$b28 000271868 7001_ $$aFarrer, Lindsay A$$b29 000271868 7001_ $$aHaines, Jonathan L$$b30 000271868 7001_ $$aByrd, Goldie S$$b31 000271868 7001_ $$aSchellenberg, Gerard D$$b32 000271868 7001_ $$aMayeux, Richard$$b33 000271868 7001_ $$aPericak-Vance, Margaret A$$b34 000271868 7001_ $$aReitz, Christiane$$b35 000271868 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz.13880$$gVol. 20, no. 8, p. 5247 - 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