title: Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk.
abstract: BACKGROUND
  African-American (AA) individuals have a higher risk for late-onset Alzheimer's disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the Alzheimer's disease (AD)-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g., APOE, ABCA7) differed substantially from previous studies in EA. There likely are risk variants of higher frequency in AAs that have not been discovered.
  
  
  METHODS
  We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status.
  
  
  RESULTS
  Compared to controls, LOAD cases showed higher levels of African ancestry, both globally and at several LOAD relevant loci, which explained risk for AD beyond global differences.
  
  
  CONCLUSIONS
  Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses.
authors.affiliation: Center for Human Genetics and Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Hohman
authors.affiliation: Center for Human Genetics and Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Jessica N
authors.initials: JN
authors.lastname: Cooke-Bailey
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Christiane
authors.initials: C
authors.lastname: Reitz
authors.affiliation: Department of Ophthalmology, 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.
authors.forename: Gyungah
authors.initials: G
authors.lastname: Jun
authors.affiliation: Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Naj
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Beecham
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Psychiatry & Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Carney
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Vance
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Psychology, College of Arts & Sciences, University of Miami, Miami, FL, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Cuccaro
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Ruchita
authors.initials: R
authors.lastname: Rajbhandary
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Badri Narayan
authors.initials: BN
authors.lastname: Vardarajan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Li-San
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Otto
authors.initials: O
authors.lastname: Valladares
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Chiao-Feng
authors.initials: CF
authors.lastname: Lin
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA; Group Health Research Institute, Group Health, Seattle, WA, USA.
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.affiliation: Department of Internal Medicine, Rush Institute for Healthy Aging, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Evans
authors.affiliation: Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham & Women's Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute, Cambridge, MA, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA; Group Health Research Institute, Group Health, Seattle, WA, USA.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
authors.affiliation: Department of Psychiatry, The Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA; Department of Genetics and Genomic Sciences, The Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA; Department of Neuroscience, The Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Jill R
authors.initials: JR
authors.lastname: Murrell
authors.affiliation: Program in Translational Neuropsychiatric Genomics, Department of Neurology, Brigham & Women's Hospital, Boston, MA, USA; Program in Medical and Population Genetics, The Broad Institute, Cambridge, MA, USA.
authors.forename: Towfique
authors.initials: T
authors.lastname: Raj
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Ertekin-Taner
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; Department of Pediatrics, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Clinton T
authors.initials: CT
authors.lastname: Baldwin
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Partners Center for Personalized Genetic Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Green
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Barnes
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Laura B
authors.initials: LB
authors.lastname: Cantwell
authors.affiliation: Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.affiliation: School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Rodney C P
authors.initials: RC
authors.lastname: Go
authors.affiliation: Division of Neurology, Department of Medicine, Morehouse School of Medicine, Atlanta, GA, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Griffith
authors.affiliation: Division of Geriatrics, Howard University Hospital, Washington, DC, USA.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Obisesan
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Manly
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA; Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA; Alzheimer's Disease Research Center, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: Department of Molecular Neuroscience, Institute of Neurology, University College of London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Indiana University Center for Aging Research, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Hugh C
authors.initials: HC
authors.lastname: Hendrie
authors.affiliation: Indiana University Center for Aging Research, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Hall
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA; Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Goate
authors.affiliation: Department of Biology, North Carolina A & T State University, Greensboro, NC, USA.
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Lang
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: 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 Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Foroud
authors.affiliation: Department of Ophthalmology, 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 Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, USA; Department of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Eden R
authors.initials: ER
authors.lastname: Martin
authors.affiliation: Dr. John T. Macdonald Foundation Department of Human Genetics, Miller School of Medicine, University of Miami, Miami, FL, USA; John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA; Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Pericak-Vance
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors.forename: Gerard D
authors.initials: GD
authors.lastname: Schellenberg
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
authors.affiliation: Center for Human Genetics and Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.affiliation: Center for Human Genetics and Research, Vanderbilt University School of Medicine, Nashville, TN, USA; Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address: t.thornton-wells@vanderbilt.edu.
authors.forename: Tricia A
authors.initials: TA
authors.lastname: Thornton-Wells
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 / Q000453:epidemiology / Q000208:ethnology* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016009:Chi-Square Distribution; D002869:Chromosome Aberrations; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000235:genetics
chemical_list: C411895:ABCA7 protein, human; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; D063268:Sialic Acid Binding Ig-like Lectin 3
keywords: Admixture mapping; African-American; Alzheimer's disease; Genome-wide association analysis (GWAS); Local admixture; Local ancestry