Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans

• DOI: 10.1016/j.jalz.2014.06.010
• Publication Date: 2014-08-27T02:45:37Z
• Authors: Mark W. Logue; Matthew Schu; Badri N. Vardarajan; John Farrell; David A. Bennett; Joseph D. Buxbaum; Goldie S. Byrd; Nilufer Ertekin‐T...; Denis Evans; Tatiana Foroud; Alison Goate; Neill R. Graff‐Ra...; M. Ilyas Kamboh; Walter A. Kukull; Jennifer J. Manly; ; Jonathan L. Haines; Richard Mayeux; Margaret A. Peric...; Gerard D. Schelle...; Kathryn L. Lunetta; Clinton T. Baldwin; M. Daniele Fallin; Lindsay A. Farrer
• Keywords: Linkage Disequilibrium; Genetic Association; Genome-wide Association Study

Abstract Background Less is known about the genetic basis of Alzheimer's disease (AD) in African Americans (AAs) than non‐Hispanic whites. Methods Whole exome sequencing (WES) was performed on seven AA AD cases. Disease association with potentially AD‐related variants from WES assessed an discovery cohort 422 cases and 394 controls. Replication sought sample 1037 1869 controls Alzheimer Genetics Consortium (ADGC). Results Forty‐four single nucleotide polymorphisms (SNPs) passed filtering criteria were successfully genotyped. Nominally significant ( P < .05) to observed two African‐descent specific AKAP9 SNPs tight linkage disequilibrium: rs144662445 = .014) rs149979685 .037). These associations replicated ADGC (rs144662445: .0022, odds ratio [OR] 2.75; rs149979685: OR 3.61). Conclusions Because not previously linked risk, this study indicates a potential new mechanism.