TY - JOUR
T1 - Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein e ε4, and the risk of late-onset Alzheimer disease in African Americans
AU - Reitz, Christiane
AU - Jun, Gyungah
AU - Naj, Adam
AU - Rajbhandary, Ruchita
AU - Vardarajan, Badri Narayan
AU - Wang, Li San
AU - Valladares, Otto
AU - Lin, Chiao Feng
AU - Larson, Eric B.
AU - Graff-Radford, Neill R.
AU - Evans, Denis
AU - De Jager, Philip L.
AU - Crane, Paul K.
AU - Buxbaum, Joseph D.
AU - Murrell, Jill R.
AU - Raj, Towfique
AU - Ertekin-Taner, Nilufer
AU - Logue, Mark
AU - Baldwin, Clinton T.
AU - Green, Robert C.
AU - Barnes, Lisa L.
AU - Cantwell, Laura B.
AU - Fallin, M. Daniele
AU - Go, Rodney C.P.
AU - Griffith, Patrick
AU - Obisesan, Thomas O.
AU - Manly, Jennifer J.
AU - Lunetta, Kathryn L.
AU - Kamboh, M. Ilyas
AU - Lopez, Oscar L.
AU - Bennett, David A.
AU - Hendrie, Hugh
AU - Hall, Kathleen S.
AU - Goate, Alison M.
AU - Byrd, Goldie S.
AU - Kukull, Walter A.
AU - Foroud, Tatiana M.
AU - Haines, Jonathan L.
AU - Farrer, Lindsay A.
AU - Pericak-Vance, Margaret A.
AU - Schellenberg, Gerard D.
AU - Mayeux, Richard
PY - 2013/4/10
Y1 - 2013/4/10
N2 - Importance: Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. Objective: To identify genetic loci associated with late-onset Alzheimer disease in African Americans. Design, Setting, and Participants: The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Main Outcomes and Measures: Presence of Alzheimer disease according to standardized criteria. Results: Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele=G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P=2.2 × 10 -9), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8<D′<0.9). The effect size for the SNP in ABCA7 was comparable with that of the APOE ε4-determining SNP rs429358 (allele=C; frequency, 0.30 cases and 0.18 controls; OR, 2.31 [95% CI, 2.19-2.42]; P=5.5 × 10-47). Several loci previously associated with Alzheimer disease but not reaching significance in genome-wide analyses were replicated in gene-based analyses accounting for linkage disequilibrium between markers and correcting for number of tests performed per gene (CR1, BIN1, EPHA1, CD33; 0.0005
AB - Importance: Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. Objective: To identify genetic loci associated with late-onset Alzheimer disease in African Americans. Design, Setting, and Participants: The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Main Outcomes and Measures: Presence of Alzheimer disease according to standardized criteria. Results: Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele=G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P=2.2 × 10 -9), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8<D′<0.9). The effect size for the SNP in ABCA7 was comparable with that of the APOE ε4-determining SNP rs429358 (allele=C; frequency, 0.30 cases and 0.18 controls; OR, 2.31 [95% CI, 2.19-2.42]; P=5.5 × 10-47). Several loci previously associated with Alzheimer disease but not reaching significance in genome-wide analyses were replicated in gene-based analyses accounting for linkage disequilibrium between markers and correcting for number of tests performed per gene (CR1, BIN1, EPHA1, CD33; 0.0005
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U2 - 10.1001/jama.2013.2973
DO - 10.1001/jama.2013.2973
M3 - Article
C2 - 23571587
AN - SCOPUS:84875922261
VL - 309
SP - 1483
EP - 1492
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
SN - 0098-7484
IS - 14
ER -