A comprehensive genetic association study of Alzheimer disease in African Americans - PubMed (original) (raw)

Comparative Study

. 2011 Dec;68(12):1569-79.

doi: 10.1001/archneurol.2011.646.

Matthew Schu, Badri N Vardarajan, Jacki Buros, Robert C Green, Rodney C P Go, Patrick Griffith, Thomas O Obisesan, Rhonna Shatz, Amy Borenstein, L Adrienne Cupples, Kathryn L Lunetta, M Daniele Fallin, Clinton T Baldwin, Lindsay A Farrer; Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study Group

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Comparative Study

A comprehensive genetic association study of Alzheimer disease in African Americans

Mark W Logue et al. Arch Neurol. 2011 Dec.

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.

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Figures

Figure 1

Figure 1

Association and linkage disequilibrium in the apolipoprotein E (APOE) region. A and B, Unadjusted findings in African Americans and whites, respectively; C and D, _APOE_-genotype adjusted findings in African Americans and whites, respectively. APOC1 indicates apolipoprotein C-I; Mb, megabase; PVRL2, poliovirus receptor–related 2; and TOMM40, translocase of outer mitochondrial membrane 40 yeast homologue.

Figure 2

Figure 2

Linkage disequilibrium in the apolipoprotein E (APOE) region. A, African American cohort data sets. B, White cohort data sets. Other gene names are described in the legend to Figure 1.

Figure 3

Figure 3

Manhattan plot of genome-wide association study results for the meta-analysis of the African American cohorts. The dotted line indicates suggestive evidence of association (P<10−5).

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