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

Mark W. Logue, Matthew Schu, Badri N. Vardarajan, John Farrell, David A. Bennett, Joseph D. Buxbaum, Goldie S. Byrd, Nilufer Ertekin-Taner, Denis Evans, Tatiana Foroud, Alison Goate, Neill R. Graff-Radford, M. Ilyas Kamboh, Walter A. Kukull, Jennifer J. Manly, Jonathan L. Hainesm, Richard Mayeuxl, Margaret A. Pericak-Vancen, Gerard D. Schellenbergo, Kathryn L. LunettabClinton T. Baldwina, M. Daniele Fallinp, Lindsay A. Farrer

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)609-618.e11
JournalAlzheimer's and Dementia
Issue number6
StatePublished - Nov 1 2014


  • AKAP9
  • African American
  • Genetic association
  • Late-onset Alzheimer's disease
  • Rare variant
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health


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