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A comprehensive genetic association study of Alzheimer disease in African Americans.

TitleA comprehensive genetic association study of Alzheimer disease in African Americans.
Publication TypeJournal Article
Year of Publication2011
AuthorsLogue, MW, Schu, M, Vardarajan, BN, Buros, J, Green, RC, Go, RCP, Griffith, P, Obisesan, TO, Shatz, R, Borenstein, A, L Cupples, A, Lunetta, KL, M Fallin, D, Baldwin, CT, Farrer, LA
Corporate AuthorsMulti-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study Group
JournalArch Neurol
Volume68
Issue12
Pagination1569-79
Date Published2011 Dec
ISSN1538-3687
KeywordsAfrican Americans, Age of Onset, Aged, Alzheimer Disease, Apolipoprotein E2, Apolipoprotein E3, Apolipoprotein E4, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Polymorphism, Single Nucleotide
Abstract

OBJECTIVES: To evaluate the association of genetic variation with late-onset Alzheimer disease (AD) in African Americans, including genes implicated in recent genome-wide association studies of whites.

DESIGN: We analyzed a genome-wide set of 2.5 million imputed markers to evaluate the genetic basis of AD in an African American population.

SUBJECTS: Five hundred thirteen well-characterized African American AD cases and 496 cognitively normal African American control subjects.

SETTING: Data were collected from multiple sites as part of the Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study and the Henry Ford Health System as part of the Genetic and Environmental Risk Factors for Alzheimer Disease Among African Americans (GenerAAtions) Study.

RESULTS: Several significant single-nucleotide polymorphisms (SNPs) were observed in the region of the apolipoprotein E gene (APOE). After adjusting for the confounding effects of APOE genotype, one of these SNPs, rs6859 in PVRL2, remained significantly associated with AD (P = .0087). Association was also observed with SNPs in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, although the effect direction for some SNPs and the most significant SNPs differed from findings in data sets consisting of whites. Finally, using the African American genome-wide association study data set as a discovery sample, we obtained suggestive evidence of association with SNPs for several novel candidate genes.

CONCLUSIONS: Some genes contribute to AD pathogenesis in both white and African American cohorts, although it is unclear whether the causal variants are the same. A larger African American sample will be needed to confirm novel gene associations, which may be population specific.

DOI10.1001/archneurol.2011.646
Alternate JournalArch. Neurol.
PubMed ID22159054
PubMed Central IDPMC3356921
Grant ListK24-AG027841 / AG / NIA NIH HHS / United States
R01-AG09029 / AG / NIA NIH HHS / United States
R01 AG009029 / AG / NIA NIH HHS / United States
U19 AG010483 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
R01-HG005092 / HG / NHGRI NIH HHS / United States
R01-AG025259 / AG / NIA NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
K24 AG027841 / AG / NIA NIH HHS / United States
P30-AG10129 / AG / NIA NIH HHS / United States
R01 HG002213 / HG / NHGRI NIH HHS / United States
K01 MH076100 / MH / NIMH NIH HHS / United States
R01 AG020688 / AG / NIA NIH HHS / United States
R01 HG005092 / HG / NHGRI NIH HHS / United States
5R01AG020688 / AG / NIA NIH HHS / United States
R01 AG025259 / AG / NIA NIH HHS / United States
R01-HG02213 / HG / NHGRI NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
P30-AG13846 / AG / NIA NIH HHS / United States