% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Ray:271868, author = {Ray, Nicholas R and Kunkle, Brian W and Hamilton-Nelson, Kara and Kurup, Jiji T and Rajabli, Farid and Qiao, Min and Vardarajan, Badri N and Cosacak, Mehmet I and Kizil, Caghan and Jean-Francois, Melissa and Cuccaro, Michael and Reyes-Dumeyer, Dolly and Cantwell, Laura and Kuzma, Amanda and Vance, Jeffery M and Gao, Sujuan and Hendrie, Hugh C and Baiyewu, Olusegun and Ogunniyi, Adesola and Akinyemi, Rufus O and Lee, Wan-Ping and Martin, Eden R and Wang, Li-San and Beecham, Gary W and Bush, William S and Xu, Wanying and Jin, Fulai and Wang, Liyong and Farrer, Lindsay A and Haines, Jonathan L and Byrd, Goldie S and Schellenberg, Gerard D and Mayeux, Richard and Pericak-Vance, Margaret A and Reitz, Christiane}, collaboration = {Consortium, Alzheimer's Disease Genetics}, title = {{E}xtended genome-wide association study employing the {A}frican genome resources panel identifies novel susceptibility loci for {A}lzheimer's disease in individuals of {A}frican ancestry.}, journal = {Alzheimer's and dementia}, volume = {20}, number = {8}, issn = {1552-5260}, address = {Hoboken, NJ}, publisher = {Wiley}, reportid = {DZNE-2024-01080}, pages = {5247 - 5261}, year = {2024}, abstract = {Despite 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.}, keywords = {Humans / Alzheimer Disease: genetics / Alzheimer Disease: ethnology / Genome-Wide Association Study / Genetic Predisposition to Disease: genetics / Black People: genetics / Linkage Disequilibrium / Polymorphism, Single Nucleotide: genetics / Female / Male / Aged / African Americans (Other) / African genome Panel (Other) / Alzheimer's disease (Other) / genome‐wide association study (Other)}, cin = {AG Kizil}, ddc = {610}, cid = {I:(DE-2719)1710007}, pnm = {352 - Disease Mechanisms (POF4-352)}, pid = {G:(DE-HGF)POF4-352}, typ = {PUB:(DE-HGF)16}, pmc = {pmc:PMC11350055}, pubmed = {pmid:38958117}, doi = {10.1002/alz.13880}, url = {https://pub.dzne.de/record/271868}, }