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Transethnic genome-wide scan identifies novel Alzheimer's disease loci.
Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse; Barber, Robert; Beecham, Gary W; Bennett, David A; Buxbaum, Joseph D; Byrd, Goldie S; Carrasquillo, Minerva M; Crane, Paul K; Cruchaga, Carlos; De Jager, Philip; Ertekin-Taner, Nilufer; Evans, Denis; Fallin, M Danielle; Foroud, Tatiana M; Friedland, Robert P; Goate, Alison M; Graff-Radford, Neill R; Hendrie, Hugh; Hall, Kathleen S; Hamilton-Nelson, Kara L; Inzelberg, Rivka; Kamboh, M Ilyas; Kauwe, John S K; Kukull, Walter A; Kunkle, Brian W; Kuwano, Ryozo; Larson, Eric B; Logue, Mark W; Manly, Jennifer J; Martin, Eden R; Montine, Thomas J; Mukherjee, Shubhabrata; Naj, Adam; Reiman, Eric M; Reitz, Christiane; Sherva, Richard; St George-Hyslop, Peter H; Thornton, Timothy; Younkin, Steven G; Vardarajan, Badri N; Wang, Li-San; Wendlund, Jens R; Winslow, Ashley R; Haines, Jonathan; Mayeux, Richard; Pericak-Vance, Margaret A; Schellenberg, Gerard; Lunetta, Kathryn L.
Afiliação
  • Jun GR; Neurogenetics and Integrated Genomics, Andover Innovative Medicines Institute, Eisai Inc, Andover, MA, USA; Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA.
  • Chung J; Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA.
  • Mez J; Department of Neurology, Boston University Schools of Medicine, Boston, MA, USA.
  • Barber R; Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA.
  • Beecham GW; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
  • Bennett DA; Department of Neurological Sciences and Rush Alzheimer's Disease Center, Chicago, IL, USA.
  • Buxbaum JD; Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA; Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA; Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA.
  • Byrd GS; Department of Biology, North Carolina A&T State University, Greensboro, NC, USA.
  • Carrasquillo MM; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Crane PK; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Cruchaga C; Hope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, MO, USA; Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
  • De Jager P; Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology & Psychiatry, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
  • Ertekin-Taner N; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Evans D; Rush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.
  • Fallin MD; Department of Mental Health, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Foroud TM; Department of Medical & Molecular Genetics, Indiana University, Indianapolis, IN, USA.
  • Friedland RP; Department of Neurology, University of Louisville, Louisville, KY, USA.
  • Goate AM; Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.
  • Graff-Radford NR; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Hendrie H; Department of Psychiatry, Indiana University, Indianapolis, IN, USA; Regenstrief Institute, Inc, Indianapolis, IN, USA.
  • Hall KS; Regenstrief Institute, Inc, Indianapolis, IN, USA; Department of Medicine, Indiana University, Indianapolis, IN, USA.
  • Hamilton-Nelson KL; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
  • Inzelberg R; Department of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
  • Kamboh MI; University of Pittsburgh Alzheimer's Disease Research Center and Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
  • Kauwe JSK; Department of Biology, Brigham Young University, Provo, UT, USA.
  • Kukull WA; Department of Epidemiology, University of Washington, Seattle, WA, USA; National Alzheimer's Coordinating Center, University of Washington, Seattle, WA, USA.
  • Kunkle BW; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
  • Kuwano R; Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan.
  • Larson EB; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA; Group Health, Group Health Research Institute, Seattle, WA, USA.
  • Logue MW; Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA; Department of Neurological Sciences and Rush Alzheimer's Disease Center, Chicago, IL, USA; National Center for PTSD, Behavioral Science Division, Boston VA Healthcare System, Boston, MA, USA.
  • Manly JJ; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
  • Martin ER; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
  • Montine TJ; Department of Pathology, Stanford University, Stanford, CA, USA.
  • Mukherjee S; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Naj A; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Reiman EM; Arizona Alzheimer's Consortium, Phoenix, AZ, USA; Department of Psychiatry, University of Arizona, Phoenix, AZ, USA; Banner Alzheimer's Institute, Phoenix, AZ, USA; Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
  • Reitz C; The Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Epidemiology, College of Physicians and Surgeons, Columbia University,
  • Sherva R; Department of Medicine (Biomedical Genetics), Boston University Schools of Medicine, Boston, MA, USA.
  • St George-Hyslop PH; Tanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Canada; Cambridge Institute for Medical Research and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
  • Thornton T; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Younkin SG; Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
  • Vardarajan BN; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Neurology, College of Physicians and Surgeons, Columbia
  • Wang LS; Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
  • Wendlund JR; PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, MA, USA.
  • Winslow AR; PharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, MA, USA.
  • Haines J; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
  • Mayeux R; The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA; The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA; The Department of Neurology, College of Physicians and Surgeons, Columbia
  • Pericak-Vance MA; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
  • Schellenberg G; Arizona Alzheimer's Consortium, Phoenix, AZ, USA.
  • Lunetta KL; Department of Biostatistics, Boston University Schools of Public Health, Boston, MA, USA.
Alzheimers Dement ; 13(7): 727-738, 2017 Jul.
Article em En | MEDLINE | ID: mdl-28183528
ABSTRACT

INTRODUCTION:

Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood.

METHODS:

We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset.

RESULTS:

Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 × 10-8) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence (P < 2.7 × 10-6) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10-6).

DISCUSSION:

Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla / Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Alzheimers Dement Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Polimorfismo de Nucleotídeo Único / Estudo de Associação Genômica Ampla / Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Alzheimers Dement Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Estados Unidos