Academic Journal
Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry
| العنوان: | Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry |
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| المؤلفون: | Ray, Nicholas R., Kunkle, Brian W., Hamilton-Nelson, Kara, Kurup, Jiji T., Rajabli, Farid, Qiao, Min, Vardarajan, Badri N., Cosacak, Mehmet I., Kizil, Caghan, Jean-Francois, Melissa, Cuccaro, Michael, Reyes-Dumeyer, Dolly, Cantwell, Laura, Kuzma, Amanda, Vance, Jeffery M., Gao, Sujuan, Hendrie, Hugh C., Baiyewu, Olusegun, Ogunniyi, Adesola, Akinyemi, Rufus O., Alzheimer’s Disease Genetics Consortium, Lee, Wan-Ping, Martin, Eden R., Wang, Li-San, Beecham, Gary W., Bush, William S., Xu, Wanying, Jin, Fulai, Wang, Liyong, Farrer, Lindsay A., Haines, Jonathan L., Byrd, Goldie S., Schellenberg, Gerard D., Mayeux, Richard, Pericak-Vance, Margaret A., Reitz, Christiane |
| المساهمون: | Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health |
| المصدر: | PMC |
| بيانات النشر: | Wiley |
| سنة النشر: | 2024 |
| المجموعة: | Indiana University - Purdue University Indianapolis: IUPUI Scholar Works |
| مصطلحات موضوعية: | African Americans, African genome panel, Alzheimer's disease, Genome‐wide association study |
| الوصف: | Introduction: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. Methods: 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. Results: 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. Discussion: 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. Highlights: 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | Alzheimer's & Dementia; https://hdl.handle.net/1805/43943 |
| الاتاحة: | https://hdl.handle.net/1805/43943 |
| Rights: | Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| رقم الانضمام: | edsbas.9F354896 |
| قاعدة البيانات: | BASE |
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