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000271868 037__ $$aDZNE-2024-01080
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000271868 1001_ $$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$$c2024
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000271868 520__ $$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.
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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 - 5261$$n8$$p5247 - 5261$$tAlzheimer's and dementia$$v20$$x1552-5260$$y2024
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