title: Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.
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.
authors: Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
authors: R S
authors: RS
authors: Desikan
authors: Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.
authors: A J
authors: AJ
authors: Schork
authors: Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.|NORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors: Y
authors: Y
authors: Wang
authors: NORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors: A
authors: A
authors: Witoelar
authors: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research University of Tubingen, Tubingen, Germany.|Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Tübingen, Germany.
authors: M
authors: M
authors: Sharma
authors: Department of Radiology, University of California, San Diego, La Jolla, CA, USA.
authors: L K
authors: LK
authors: McEvoy
authors: Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
authors: D
authors: D
authors: Holland
authors: Department of Radiology, University of California, San Diego, La Jolla, CA, USA.|Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.
authors: J B
authors: JB
authors: Brewer
authors: Department of Radiology, University of California, San Diego, La Jolla, CA, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors: C-H
authors: CH
authors: Chen
authors: Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors: W K
authors: WK
authors: Thompson
authors: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, UK.
authors: D
authors: D
authors: Harold
authors: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, UK.
authors: J
authors: J
authors: Williams
authors: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, UK.
authors: M J
authors: MJ
authors: Owen
authors: Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Wales, UK.
authors: M C
authors: MC
authors: O'Donovan
authors: The John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
authors: M A
authors: MA
authors: Pericak-Vance
authors: Department of Neurology, Taub Institute on Alzheimer's Disease and the Aging Brain, and Gertrude H. Sergievsky Center, Columbia University, New York, NY, USA.
authors: R
authors: R
authors: Mayeux
authors: Department of Molecular Physiology and Biophysics, Vanderbilt Center for Human Genetics Research, Vanderbilt University, Nashville, TN, USA.
authors: J L
authors: JL
authors: Haines
authors: Departments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Biostatistics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA.
authors: L A
authors: LA
authors: Farrer
authors: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
authors: G D
authors: GD
authors: Schellenberg
authors: German Center for Neurodegenerative Diseases (DZNE)-Tübingen, Paul-Ehrlich-Straße 15, Tübingen, Germany.
authors: P
authors: P
authors: Heutink
authors: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
authors: A B
authors: AB
authors: Singleton
authors: Sorbonne Université, UPMC Univ Paris 06, Paris, France.
authors: A
authors: A
authors: Brice
authors: UCL Genetics Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors: N W
authors: NW
authors: Wood
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors: J
authors: J
authors: Hardy
authors: INSERM UMR1043, CPTP, CHU Purpan, Toulouse, France.
authors: M
authors: http://orcid.org/0000-0003-2180-4537
authors: M
authors: Martinez
authors: Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.
authors: S H
authors: SH
authors: Choi
authors: Department of Biostatistics, School of Public Health, Boston University, Boston, MA, USA.|The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
authors: A
authors: A
authors: DeStefano
authors: Deparment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
authors: M A
authors: http://orcid.org/0000-0003-0372-8585
authors: MA
authors: Ikram
authors: Deparment of Internal Medicine, University of Washington, Seattle, WA, USA.
authors: J C
authors: JC
authors: Bis
authors: Icelandic Heart Association, Kopavogur, Iceland.
authors: A
authors: A
authors: Smith
authors: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors: A L
authors: AL
authors: Fitzpatrick
authors: Laboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Washington, DC, USA.
authors: L
authors: L
authors: Launer
authors: Deparment of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Netherlands.
authors: C
authors: C
authors: van Duijn
authors: The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.|Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
authors: S
authors: S
authors: Seshadri
authors: Norwegian Centre for Dementia Research, Department of Old Age Psychiatry, Oslo University Hospital, Oslo, Norway.
authors: I D
authors: ID
authors: Ulstein
authors: Department of Geriatric Psychiatry, Akershus University Hospital, Oslo, Norway.|Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.|Alzheimer's Disease Research Centre, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
authors: D
authors: D
authors: Aarsland
authors: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Neurology, Akershus University Hospital, Oslo, Norway.
authors: T
authors: T
authors: Fladby
authors: NORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors: S
authors: S
authors: Djurovic
authors: Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
authors: B T
authors: BT
authors: Hyman
authors: Department of Geriatric Medicine, University Hospital Reykjavik, Reykjavik, Iceland.
authors: J
authors: J
authors: Snaedal
authors: deCODE Genetics/Amgen, Reykjavik, Iceland.
authors: H
authors: H
authors: Stefansson
authors: deCODE Genetics/Amgen, Reykjavik, Iceland.|Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors: K
authors: K
authors: Stefansson
authors: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research University of Tubingen, Tubingen, Germany.
authors: T
authors: T
authors: Gasser
authors: NORMENT; Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors: O A
authors: OA
authors: Andreassen
authors: Department of Radiology, University of California, San Diego, La Jolla, CA, USA.|Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA.|Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA.|Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
authors: A M
authors: AM
authors: Dale
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D005260:Female; D056426:Genetic Loci; D058685:Genetic Pleiotropy; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D016875:tau Proteins / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; C054369:MAPT protein, human; D016875:tau Proteins