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Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease.
Lunnon, Katie; Smith, Rebecca; Hannon, Eilis; De Jager, Philip L; Srivastava, Gyan; Volta, Manuela; Troakes, Claire; Al-Sarraj, Safa; Burrage, Joe; Macdonald, Ruby; Condliffe, Daniel; Harries, Lorna W; Katsel, Pavel; Haroutunian, Vahram; Kaminsky, Zachary; Joachim, Catharine; Powell, John; Lovestone, Simon; Bennett, David A; Schalkwyk, Leonard C; Mill, Jonathan.
Affiliation
  • Lunnon K; University of Exeter Medical School, Exeter University, Exeter, UK.
  • Smith R; Institute of Psychiatry, King's College London, London, UK.
  • Hannon E; University of Exeter Medical School, Exeter University, Exeter, UK.
  • De Jager PL; 1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Ins
  • Srivastava G; 1] Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute, Cambridge, USA.
  • Volta M; Institute of Psychiatry, King's College London, London, UK.
  • Troakes C; Institute of Psychiatry, King's College London, London, UK.
  • Al-Sarraj S; Institute of Psychiatry, King's College London, London, UK.
  • Burrage J; University of Exeter Medical School, Exeter University, Exeter, UK.
  • Macdonald R; University of Exeter Medical School, Exeter University, Exeter, UK.
  • Condliffe D; Institute of Psychiatry, King's College London, London, UK.
  • Harries LW; University of Exeter Medical School, Exeter University, Exeter, UK.
  • Katsel P; Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, USA.
  • Haroutunian V; 1] Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, USA. [2] Department of Neuroscience, The Icahn School of Medicine at Mount Sinai, New York, USA. [3] JJ Peters Virginia Medical Center, Bronx, New York, USA.
  • Kaminsky Z; 1] Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • Joachim C; Department of Neuropathology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
  • Powell J; Institute of Psychiatry, King's College London, London, UK.
  • Lovestone S; 1] Institute of Psychiatry, King's College London, London, UK. [2] Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, UK.
  • Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
  • Schalkwyk LC; 1] Institute of Psychiatry, King's College London, London, UK. [2].
  • Mill J; 1] University of Exeter Medical School, Exeter University, Exeter, UK. [2] Institute of Psychiatry, King's College London, London, UK. [3].
Nat Neurosci ; 17(9): 1164-70, 2014 Sep.
Article in En | MEDLINE | ID: mdl-25129077
Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is characterized by progressive neuropathology and cognitive decline. We performed a cross-tissue analysis of methylomic variation in AD using samples from four independent human post-mortem brain cohorts. We identified a differentially methylated region in the ankyrin 1 (ANK1) gene that was associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as being substantially hypermethylated in two other cortical regions (superior temporal gyrus and prefrontal cortex), but not in the cerebellum, a region largely protected from neurodegeneration in AD, or whole blood obtained pre-mortem from the same individuals. Neuropathology-associated ANK1 hypermethylation was subsequently confirmed in cortical samples from three independent brain cohorts. This study represents, to the best of our knowledge, the first epigenome-wide association study of AD employing a sequential replication design across multiple tissues and highlights the power of this approach for identifying methylomic variation associated with complex disease.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cerebral Cortex / Ankyrins / DNA Methylation / Alzheimer Disease Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Nat Neurosci Journal subject: NEUROLOGIA Year: 2014 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Cerebral Cortex / Ankyrins / DNA Methylation / Alzheimer Disease Limits: Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Nat Neurosci Journal subject: NEUROLOGIA Year: 2014 Document type: Article Country of publication: United States