dc.contributor.author | Lunnon, Katie | |
dc.contributor.author | Smith, Rebecca | |
dc.contributor.author | Hannon, E | |
dc.contributor.author | De Jager, PL | |
dc.contributor.author | Srivastava, G.P. | |
dc.contributor.author | Volta, M | |
dc.contributor.author | Troakes, C | |
dc.contributor.author | Al-Sarraj, S | |
dc.contributor.author | Burrage, J | |
dc.contributor.author | Macdonald, Ruby | |
dc.contributor.author | Condliffe, Daniel | |
dc.contributor.author | Harries, LW | |
dc.contributor.author | Katsel, Pavel | |
dc.contributor.author | Haroutunian, Vahram | |
dc.contributor.author | Kaminsky, Zachary | |
dc.contributor.author | Joachim, Catharine | |
dc.contributor.author | Powell, J | |
dc.contributor.author | Lovestone, Simon | |
dc.contributor.author | Bennett, DA | |
dc.contributor.author | Schalkwyk, Leonard | |
dc.contributor.author | Mill, J | |
dc.date.accessioned | 2016-02-05T14:00:45Z | |
dc.date.issued | 2014-08-17 | |
dc.description.abstract | 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. | en_GB |
dc.description.sponsorship | US National Institutes of Health | en_GB |
dc.description.sponsorship | Alzheimer's Research UK | en_GB |
dc.description.sponsorship | Department of Veterans Affairs | en_GB |
dc.identifier.citation | Vol. 17, pp. 1164 - 1170 | en_GB |
dc.identifier.doi | 10.1038/nn.3782 | |
dc.identifier.grantnumber | R01 AG036039 | en_GB |
dc.identifier.grantnumber | Equipment Grant | en_GB |
dc.identifier.grantnumber | AG02219 | en_GB |
dc.identifier.grantnumber | AG05138 | en_GB |
dc.identifier.grantnumber | MH064673 | en_GB |
dc.identifier.grantnumber | VISN3 MIRECC | en_GB |
dc.identifier.grantnumber | R01 AG036042 | en_GB |
dc.identifier.grantnumber | R01AG036836 | en_GB |
dc.identifier.grantnumber | R01 AG17917 | en_GB |
dc.identifier.grantnumber | R01 AG15819 | en_GB |
dc.identifier.grantnumber | R01 AG032990 | en_GB |
dc.identifier.grantnumber | R01 AG18023 | en_GB |
dc.identifier.grantnumber | RC2 AG036547 | en_GB |
dc.identifier.grantnumber | P30 AG10161 | en_GB |
dc.identifier.grantnumber | P50 AG016574 | en_GB |
dc.identifier.grantnumber | U01 ES017155 | en_GB |
dc.identifier.grantnumber | KL2 RR024151 | en_GB |
dc.identifier.grantnumber | K25 AG041906-01 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/19629 | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Publishing Group | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/25129077 | en_GB |
dc.subject | Aged | en_GB |
dc.subject | Aged, 80 and over | en_GB |
dc.subject | Alzheimer Disease | en_GB |
dc.subject | Ankyrins | en_GB |
dc.subject | Cerebral Cortex | en_GB |
dc.subject | DNA Methylation | en_GB |
dc.subject | Entorhinal Cortex | en_GB |
dc.subject | Epigenesis, Genetic | en_GB |
dc.subject | Female | en_GB |
dc.subject | Genome-Wide Association Study | en_GB |
dc.subject | Humans | en_GB |
dc.subject | Male | en_GB |
dc.subject | Middle Aged | en_GB |
dc.subject | Prefrontal Cortex | en_GB |
dc.subject | Temporal Lobe | en_GB |
dc.subject | Transcriptome | en_GB |
dc.title | Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2016-02-05T14:00:45Z | |
dc.identifier.issn | 1097-6256 | |
exeter.place-of-publication | United States | |
dc.identifier.eissn | 1546-1726 | |
dc.identifier.journal | Nature Neuroscience | en_GB |