Alzheimer's & dementia : the journal of the Alzheimer's Association · 2014
Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans.
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Logue Mark W, Schu Matthew, Vardarajan Badri N, Farrell John, Bennett David A, Buxbaum Joseph D, Byrd Goldie S, Ertekin-Taner Nilufer, Evans Denis, Foroud Tatiana, Goate Alison, Graff-Radford Neill R, Kamboh M Ilyas, Kukull Walter A, Manly Jennifer J, Alzheimer Disease Genetics Consortium, Alzheimer Disease Genetics Consortium
Аннотация
BACKGROUND: Less is known about the genetic basis of Alzheimer's disease (AD) in African Americans (AAs) than in non-Hispanic whites.
METHODS: Whole exome sequencing (WES) was performed on seven AA AD cases. Disease association with potentially AD-related variants from WES was assessed in an AA discovery cohort of 422 cases and 394 controls. Replication was sought in an AA sample of 1037 cases and 1869 controls from the Alzheimer Disease Genetics Consortium (ADGC).
RESULTS: Forty-four single nucleotide polymorphisms (SNPs) from WES passed filtering criteria and were successfully genotyped. Nominally significant (P < .05) association to AD was observed with two African-descent specific AKAP9 SNPs in tight linkage disequilibrium: rs144662445 (P = .014) and rs149979685 (P = .037). These associations were replicated in the ADGC sample (rs144662445: P = .0022, odds ratio [OR] = 2.75; rs149979685: P = .0022, OR = 3.61).
CONCLUSIONS: Because AKAP9 was not previously linked to AD risk, this study indicates a potential new disease mechanism.
METHODS: Whole exome sequencing (WES) was performed on seven AA AD cases. Disease association with potentially AD-related variants from WES was assessed in an AA discovery cohort of 422 cases and 394 controls. Replication was sought in an AA sample of 1037 cases and 1869 controls from the Alzheimer Disease Genetics Consortium (ADGC).
RESULTS: Forty-four single nucleotide polymorphisms (SNPs) from WES passed filtering criteria and were successfully genotyped. Nominally significant (P < .05) association to AD was observed with two African-descent specific AKAP9 SNPs in tight linkage disequilibrium: rs144662445 (P = .014) and rs149979685 (P = .037). These associations were replicated in the ADGC sample (rs144662445: P = .0022, odds ratio [OR] = 2.75; rs149979685: P = .0022, OR = 3.61).
CONCLUSIONS: Because AKAP9 was not previously linked to AD risk, this study indicates a potential new disease mechanism.