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Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium.
Hohman, Timothy J; Bush, William S; Jiang, Lan; Brown-Gentry, Kristin D; Torstenson, Eric S; Dudek, Scott M; Mukherjee, Shubhabrata; Naj, Adam; Kunkle, Brian W; Ritchie, Marylyn D; Martin, Eden R; Schellenberg, Gerard D; Mayeux, Richard; Farrer, Lindsay A; Pericak-Vance, Margaret A; Haines, Jonathan L; Thornton-Wells, Tricia A.
Afiliación
  • Hohman TJ; Vanderbilt Memory & Alzheimer's Center, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Bush WS; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
  • Jiang L; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Brown-Gentry KD; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Torstenson ES; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Dudek SM; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Mukherjee S; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Naj A; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA.
  • Kunkle BW; Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA.
  • Ritchie MD; Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.
  • Martin ER; Dr. John T. Macdonald Foundation Department of Human Genetics and 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.
  • Schellenberg GD; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Mayeux R; Gertrude H. Sergievsky Center, Department of Neurology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
  • Farrer LA; Department of Medicine (Biomedical Genetics), Boston University, Boston, MA, USA; Department of Neurology, Boston University, Boston, MA, USA; Department of Ophthalmology, Boston University, Boston, MA, USA; Department of Epidemiology, Boston University, Boston, MA, USA; Department of Biostatistics,
  • Pericak-Vance MA; Dr. John T. Macdonald Foundation Department of Human Genetics and 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.
  • Haines JL; Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
  • Thornton-Wells TA; Vanderbilt Genetics Institute, Department of Molecular Physiology & Biophysics, Vanderbilt University Medical Center, Nashville, TN, USA. Electronic address: triciathorntonwells@gmail.com.
Neurobiol Aging ; 38: 141-150, 2016 Feb.
Article en En | MEDLINE | ID: mdl-26827652
Late-onset Alzheimer disease (AD) has a complex genetic etiology, involving locus heterogeneity, polygenic inheritance, and gene-gene interactions; however, the investigation of interactions in recent genome-wide association studies has been limited. We used a biological knowledge-driven approach to evaluate gene-gene interactions for consistency across 13 data sets from the Alzheimer Disease Genetics Consortium. Fifteen single nucleotide polymorphism (SNP)-SNP pairs within 3 gene-gene combinations were identified: SIRT1 × ABCB1, PSAP × PEBP4, and GRIN2B × ADRA1A. In addition, we extend a previously identified interaction from an endophenotype analysis between RYR3 × CACNA1C. Finally, post hoc gene expression analyses of the implicated SNPs further implicate SIRT1 and ABCB1, and implicate CDH23 which was most recently identified as an AD risk locus in an epigenetic analysis of AD. The observed interactions in this article highlight ways in which genotypic variation related to disease may depend on the genetic context in which it occurs. Further, our results highlight the utility of evaluating genetic interactions to explain additional variance in AD risk and identify novel molecular mechanisms of AD pathogenesis.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Epistasis Genética / Estudios de Asociación Genética / Enfermedad de Alzheimer / Conjuntos de Datos como Asunto Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Neurobiol Aging Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Epistasis Genética / Estudios de Asociación Genética / Enfermedad de Alzheimer / Conjuntos de Datos como Asunto Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Female / Humans / Male Idioma: En Revista: Neurobiol Aging Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos