title: Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans.
abstract: African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.
  
  
  
  We conducted a genome-wide association study (GWAS) in AAs employing informed conditioning in 1825 LOAD cases and 3784 cognitively normal controls. We derived a posterior liability conditioned on age, sex, diabetes status, current smoking status, educational attainment, and affection status, with parameters informed by external prevalence information. We assessed association between the posterior liability and a genome-wide set of single-nucleotide polymorphisms (SNPs), controlling for APOE and ABCA7, identified previously in a LOAD GWAS of AAs.
  
  
  
  Two SNPs at novel loci, rs112404845 (P = 3.8 × 10-8), upstream of COBL, and rs16961023 (P = 4.6 × 10-8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability.
  
  
  
  An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.
authors: Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA. Electronic address: jessemez@bu.edu.
authors: Jesse
authors: J
authors: Mez
authors: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
authors: Jaeyoon
authors: J
authors: Chung
authors: 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; Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA.
authors: Gyungah
authors: G
authors: Jun
authors: Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.
authors: Joshua
authors: J
authors: Kriegel
authors: Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA.
authors: Alexandra P
authors: AP
authors: Bourlas
authors: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
authors: Richard
authors: R
authors: Sherva
authors: 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: Mark W
authors: MW
authors: Logue
authors: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors: Lisa L
authors: LL
authors: Barnes
authors: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
authors: David A
authors: DA
authors: Bennett
authors: Departments of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors: Joseph D
authors: JD
authors: Buxbaum
authors: Department of Biology, North Carolina A & T State University, Greensboro, NC, USA.
authors: Goldie S
authors: GS
authors: Byrd
authors: Department of Medicine, University of Washington, Seattle, WA, USA.
authors: Paul K
authors: PK
authors: Crane
authors: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors: Nilüfer
authors: N
authors: Ertekin-Taner
authors: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors: Denis
authors: D
authors: Evans
authors: Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, MD, USA; Department of Biostatistics, Johns Hopkins School of Public Health, Baltimore, MD, USA; Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD, USA.
authors: M Daniele
authors: MD
authors: Fallin
authors: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Tatiana
authors: T
authors: Foroud
authors: Departments of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
authors: Alison
authors: A
authors: Goate
authors: Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors: Neill R
authors: NR
authors: Graff-Radford
authors: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
authors: Kathleen S
authors: KS
authors: Hall
authors: Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
authors: M Ilyas
authors: MI
authors: Kamboh
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors: Walter A
authors: WA
authors: Kukull
authors: Group Health, Group Health Research Institute, Seattle, WA, USA.
authors: Eric B
authors: EB
authors: Larson
authors: Department of Neurology and the Taub Institute, Columbia University, New York, NY, USA.
authors: Jennifer J
authors: JJ
authors: Manly
authors: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors: Jonathan L
authors: JL
authors: Haines
authors: Department of Neurology and the Taub Institute, Columbia University, New York, NY, USA.
authors: Richard
authors: R
authors: Mayeux
authors: The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
authors: Margaret A
authors: MA
authors: Pericak-Vance
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors: Gerard D
authors: GD
authors: Schellenberg
authors: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors: Kathryn L
authors: KL
authors: Lunetta
authors: Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, MA, USA; 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; Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
authors: Lindsay A
authors: LA
authors: Farrer
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000208:ethnology* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D048909:Diabetes Complications / Q000208:ethnology / Q000235:genetics; D004522:Educational Status; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012907:Smoking / Q000208:ethnology / Q000235:genetics; D027981:Symporters / Q000235:genetics*
chemical_list: C411895:ABCA7 protein, human; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; C561633:Cobl protein, human; D008840:Microfilament Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter
keywords: ABCA7; APOE; African Americans; Age; Alzheimer's disease; COBL; Diabetes; Education; Genome-wide association study (GWAS); Informed conditioning on clinical covariates; Resveratrol; SLC10A2; Sex differences; Smoking