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Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans.
Mez, Jesse; Chung, Jaeyoon; Jun, Gyungah; Kriegel, Joshua; Bourlas, Alexandra P; Sherva, Richard; Logue, Mark W; Barnes, Lisa L; Bennett, David A; Buxbaum, Joseph D; Byrd, Goldie S; Crane, Paul K; Ertekin-Taner, Nilüfer; Evans, Denis; Fallin, M Daniele; Foroud, Tatiana; Goate, Alison; Graff-Radford, Neill R; Hall, Kathleen S; Kamboh, M Ilyas; Kukull, Walter A; Larson, Eric B; Manly, Jennifer J; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Schellenberg, Gerard D; Lunetta, Kathryn L; Farrer, Lindsay A.
Afiliação
  • Mez J; 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.
  • Chung J; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
  • Jun G; 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.
  • Kriegel J; 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.
  • Bourlas AP; 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.
  • Sherva R; Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
  • Logue MW; 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.
  • Barnes LL; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
  • Bennett DA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
  • Buxbaum JD; 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.
  • Byrd GS; Department of Biology, North Carolina A & T State University, Greensboro, NC, USA.
  • Crane PK; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Ertekin-Taner N; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
  • Evans D; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
  • Fallin MD; 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.
  • Foroud T; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Goate A; 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.
  • Graff-Radford NR; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
  • Hall KS; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Kamboh MI; Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
  • Kukull WA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Larson EB; Group Health, Group Health Research Institute, Seattle, WA, USA.
  • Manly JJ; Department of Neurology and the Taub Institute, Columbia University, New York, NY, USA.
  • Haines JL; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
  • Mayeux R; Department of Neurology and the Taub Institute, Columbia University, New York, NY, USA.
  • Pericak-Vance MA; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
  • Schellenberg GD; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Lunetta KL; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Farrer LA; 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,
Alzheimers Dement ; 13(2): 119-129, 2017 02.
Article em En | MEDLINE | ID: mdl-27770636
ABSTRACT

INTRODUCTION:

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.

METHODS:

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.

RESULTS:

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.

DISCUSSION:

An informed conditioning approach can detect LOAD genetic associations in AAs not identified by traditional GWAS.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Negro ou Afro-Americano / Polimorfismo de Nucleotídeo Único / Transportadores de Ânions Orgânicos Dependentes de Sódio / Simportadores / Loci Gênicos / Doença de Alzheimer / Proteínas dos Microfilamentos Tipo de estudo: Prevalence_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Negro ou Afro-Americano / Polimorfismo de Nucleotídeo Único / Transportadores de Ânions Orgânicos Dependentes de Sódio / Simportadores / Loci Gênicos / Doença de Alzheimer / Proteínas dos Microfilamentos Tipo de estudo: Prevalence_studies / Risk_factors_studies Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Ano de publicação: 2017 Tipo de documento: Article