Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk.

Hohman TJ, Cooke-Bailey JN, Reitz C, Jun G, Naj A, Beecham GW, Liu Z, Carney RM, Vance JM, Cuccaro ML, Rajbhandary R, Vardarajan BN, Wang LS, Valladares O, Lin CF, Larson EB, Graff-Radford NR, Evans D, De Jager PL, Crane PK, Buxbaum JD, Murrell JR, Raj T, Ertekin-Taner N, Logue MW, Baldwin CT, Green RC, Barnes LL, Cantwell LB, Fallin MD, Go RC, Griffith P, Obisesan TO, Manly JJ, Lunetta KL, Kamboh MI, Lopez OL, Bennett DA, Hardy J, Hendrie HC, Hall KS, Goate AM, Lang R, Byrd GS, Kukull WA, Foroud TM, Farrer LA, Martin ER, Pericak-Vance MA, Schellenberg GD, Mayeux R, Haines JL, Thornton-Wells TA, Alzheimer Disease Genetics Consortium
Alzheimers Dement. 2016 12 (3): 233-43

PMID: 26092349 · PMCID: PMC4681680 · DOI:10.1016/j.jalz.2015.02.012

INTRODUCTION - African-American (AA) individuals have a higher risk for late-onset Alzheimer's disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the Alzheimer's disease (AD)-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g., APOE, ABCA7) differed substantially from previous studies in EA. There likely are risk variants of higher frequency in AAs that have not been discovered.

METHODS - We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status.

RESULTS - Compared to controls, LOAD cases showed higher levels of African ancestry, both globally and at several LOAD relevant loci, which explained risk for AD beyond global differences.

DISCUSSION - Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses.

Copyright © 2016 The Alzheimer's Association. All rights reserved.

MeSH Terms (17)

African Americans Aged Aged, 80 and over Alzheimer Disease Apolipoproteins E ATP-Binding Cassette Transporters Chi-Square Distribution Chromosome Aberrations Cohort Studies Female Genetic Association Studies Genetic Predisposition to Disease Genotype Humans Male Polymorphism, Single Nucleotide Sialic Acid Binding Ig-like Lectin 3

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