Premium
Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans
Author(s) -
Logue Mark W.,
Schu Matthew,
Vardarajan Badri N.,
Farrell John,
Bennett David A.,
Buxbaum Joseph D.,
Byrd Goldie S.,
ErtekinTaner Nilufer,
Evans Denis,
Foroud Tatiana,
Goate Alison,
GraffRadford Neill R.,
Kamboh M. Ilyas,
Kukull Walter A.,
Manly Jennifer J.,
Haines Jonathan L.,
Mayeux Richard,
PericakVance Margaret A.,
Schellenberg Gerard D.,
Lunetta Kathryn L.,
Baldwin Clinton T.,
Fallin M. Daniele,
Farrer Lindsay A.
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.06.010
Subject(s) - linkage disequilibrium , single nucleotide polymorphism , odds ratio , disease , exome sequencing , genetics , genetic association , genome wide association study , alzheimer's disease , biology , medicine , genotype , gene , mutation
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.