Your browser doesn't support javascript.
loading
Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.
Desikan, R S; Schork, A J; Wang, Y; Witoelar, A; Sharma, M; McEvoy, L K; Holland, D; Brewer, J B; Chen, C-H; Thompson, W K; Harold, D; Williams, J; Owen, M J; O'Donovan, M C; Pericak-Vance, M A; Mayeux, R; Haines, J L; Farrer, L A; Schellenberg, G D; Heutink, P; Singleton, A B; Brice, A; Wood, N W; Hardy, J; Martinez, M; Choi, S H; DeStefano, A; Ikram, M A; Bis, J C; Smith, A; Fitzpatrick, A L; Launer, L; van Duijn, C; Seshadri, S; Ulstein, I D; Aarsland, D; Fladby, T; Djurovic, S; Hyman, B T; Snaedal, J; Stefansson, H; Stefansson, K; Gasser, T; Andreassen, O A; Dale, A M.
Affiliation
  • Desikan RS; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
  • Schork AJ; Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.
  • Wang Y; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Witoelar A; NORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • Sharma M; NORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • McEvoy LK; Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research University of Tubingen, Tubingen, Germany.
  • Holland D; Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
  • Brewer JB; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
  • Chen CH; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Thompson WK; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
  • Harold D; Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
  • Williams J; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
  • Owen MJ; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • O'Donovan MC; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
  • Pericak-Vance MA; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, UK.
  • Mayeux R; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, UK.
  • Haines JL; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, UK.
  • Farrer LA; Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, UK.
  • Schellenberg GD; The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
  • Heutink P; Department of Neurology, Taub Institute on Alzheimer's Disease and the Aging Brain, and Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA.
  • Singleton AB; Department of Molecular Physiology and Biophysics, Vanderbilt Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA.
  • Brice A; Departments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Biostatistics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA.
  • Wood NW; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
  • Hardy J; German Center for Neurodegenerative Diseases (DZNE)-Tübingen, Paul-Ehrlich-Straße 15, Tübingen, Germany.
  • Martinez M; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
  • Choi SH; Sorbonne Université, UPMC Univ Paris 06, Paris, France.
  • DeStefano A; UCL Genetics Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
  • Ikram MA; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
  • Bis JC; INSERM UMR1043, CPTP, CHU Purpan, Toulouse, France.
  • Smith A; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
  • Fitzpatrick AL; Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
  • Launer L; The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
  • van Duijn C; Deparment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
  • Seshadri S; Deparment of Internal Medicine, University of Washington, Seattle, WA, USA.
  • Ulstein ID; Icelandic Heart Association, Kopavogur, Iceland.
  • Aarsland D; Department of Epidemiology, University of Washington, Seattle, WA, USA.
  • Fladby T; Laboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Washington, DC, USA.
  • Djurovic S; Deparment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
  • Hyman BT; The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
  • Snaedal J; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
  • Stefansson H; Norwegian Centre for Dementia Research, Department of Old Age Psychiatry, Oslo University Hospital, Oslo, Norway.
  • Stefansson K; Department of Geriatric Psychiatry, Akershus University Hospital, Oslo, Norway.
  • Gasser T; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
  • Andreassen OA; Alzheimer's Disease Research Centre, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
  • Dale AM; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Mol Psychiatry ; 20(12): 1588-95, 2015 Dec.
Article in En | MEDLINE | ID: mdl-25687773
ABSTRACT
We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.
Subject(s)
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Parkinson Disease / Tau Proteins / Alzheimer Disease Type of study: Prognostic_studies Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Mol Psychiatry Journal subject: BIOLOGIA MOLECULAR / PSIQUIATRIA Year: 2015 Type: Article Affiliation country: United States
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Parkinson Disease / Tau Proteins / Alzheimer Disease Type of study: Prognostic_studies Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Mol Psychiatry Journal subject: BIOLOGIA MOLECULAR / PSIQUIATRIA Year: 2015 Type: Article Affiliation country: United States