title: Two rare AKAP9 variants are associated with Alzheimer's disease in African Americans.
abstract: 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.
authors.affiliation: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Logue
authors.affiliation: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Schu
authors.affiliation: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
authors.forename: Badri N
authors.initials: BN
authors.lastname: Vardarajan
authors.affiliation: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Farrell
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: Departments of Neuroscience and Genetics & Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
authors.affiliation: Department of Biology, North Carolina A & T State University, Greensboro, NC, USA.
authors.forename: Goldie S
authors.initials: GS
authors.lastname: Byrd
authors.affiliation: Departments of Neuroscience and Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Ertekin-Taner
authors.affiliation: Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Evans
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University, Indianapolis, IN, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.affiliation: Department of Psychiatry and Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St. Louis, MI, USA.
authors.forename: Alison
authors.initials: A
authors.lastname: Goate
authors.affiliation: Departments of Neuroscience and Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.affiliation: Department of Human Genetics and Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
authors.affiliation: National Alzheimer's Coordinating Center and Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Kukull
authors.affiliation: Department of Neurology and the Taub Institute, Columbia University, New York, NY, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Manly
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics*; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology* / Q000235:genetics*; D016000:Cluster Analysis; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D054758:A Kinase Anchor Proteins; C119719:AKAP9 protein, human; D003598:Cytoskeletal Proteins
keywords: AKAP9; African American; Genetic association; Late-onset Alzheimer's disease; Rare variant; Whole-exome sequencing