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Title | Admixture mapping identifies novel Alzheimer's disease risk regions in African Americans. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Rajabli F, Tosto G, Hamilton-Nelson KL, Kunkle BW, Vardarajan BN, Naj A, Whitehead PG, Gardner OK, Bush WS, Sariya S, Mayeux RP, Farrer LA, Cuccaro ML, Vance JM, Griswold AJ, Schellenberg GD, Haines JL, Byrd GS, Reitz C, Beecham GW, Pericak-Vance MA, Martin ER |
Corporate Authors | Alzheimer's Disease Genetics Consortium(ADGC), Collaboration on Alzheimer's Disease Research(CADRE) and Alzheimer's Disease Sequencing Project(ADSP) |
Journal | Alzheimers Dement |
Date Published | 12/2022 |
ISSN | 1552-5279 |
Abstract | BACKGROUND: This study used admixture mapping to prioritize the genetic regions associated with Alzheimer's disease (AD) in African American (AA) individuals, followed by ancestry-aware regression analysis to fine-map the prioritized regions. METHODS: We analyzed 10,271 individuals from 17 different AA datasets. We performed admixture mapping and meta-analyzed the results. We then used regression analysis, adjusting for local ancestry main effects and interactions with genotype, to refine the regions identified from admixture mapping. Finally, we leveraged in silico annotation and differential gene expression data to prioritize AD-related variants and genes. RESULTS: Admixture mapping identified two genome-wide significant loci on chromosomes 17p13.2 (p = 2.2 × 10 ) and 18q21.33 (p = 1.2 × 10 ). Our fine mapping of the chromosome 17p13.2 and 18q21.33 regions revealed several interesting genes such as the MINK1, KIF1C, and BCL2. DISCUSSION: Our ancestry-aware regression approach showed that AA individuals have a lower risk of AD if they inherited African ancestry admixture block at the 17p13.2 locus. HIGHLIGHTS: We identified two genome-wide significant admixture mapping signals: on chromosomes 17p13.2 and 18q21.33, which are novel in African American (AA) populations. Our ancestry-aware regression approach showed that AA individuals have a lower risk of Alzheimer's disease (AD) if they inherited African ancestry admixture block at the 17p13.2 locus. We found that the overall proportion of African ancestry does not differ between the cases and controls that suggest African genetic ancestry alone is not likely to explain the AD prevalence difference between AA and non-Hispanic White populations. |
DOI | 10.1002/alz.12865 |
Alternate Journal | Alzheimers Dement |
PubMed ID | 36539198 |
Grant List | AG058654 / AG / NIA NIH HHS / United States AG16002 / AG / NIA NIH HHS / United States AG032984 / AG / NIA NIH HHS / United States AG052410 / AG / NIA NIH HHS / United States AG070864 / AG / NIA NIH HHS / United States U01 AG058654 / AG / NIA NIH HHS / United States R01 AG062634 / AG / NIA NIH HHS / United States AG057659 / AG / NIA NIH HHS / United States AG072547 / AG / NIA NIH HHS / United States |