TY - JOUR
T1 - A comprehensive genetic association study of Alzheimer disease in African Americans
AU - Logue, Mark W.
AU - Schu, Matthew
AU - Vardarajan, Badri N.
AU - Buros, Jacki
AU - Green, Robert C.
AU - Go, Rodney C.P.
AU - Griffith, Patrick
AU - Obisesan, Thomas O.
AU - Shatz, Rhonna
AU - Borenstein, Amy
AU - Cupples, L. Adrienne
AU - Lunetta, Kathryn L.
AU - Fallin, Daniele M.
AU - Baldwin, Clinton T.
AU - Farrer, Lindsay A.
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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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U2 - 10.1001/archneurol.2011.646
DO - 10.1001/archneurol.2011.646
M3 - Article
C2 - 22159054
AN - SCOPUS:83455211863
SN - 0003-9942
VL - 68
SP - 1569
EP - 1579
JO - Archives of neurology
JF - Archives of neurology
IS - 12
ER -