Cross-tissue methylomic profiling strongly implicates a role for cortex-specific deregulation of ANK1 in Alzheimer’s disease neuropathology
| Autor: | Lunnon, Katie, Smith, Rebecca, Hannon, Eilis, De Jager, Philip, 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, Mill, Jonathan |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: | |
| Zdroj: | Nature neuroscience |
| ISSN: | 1546-1726 1097-6256 |
| Popis: | Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by progressive neuropathology and cognitive decline. We describe a cross-tissue analysis of methylomic variation in AD using samples from three independent human post-mortem brain cohorts. We identify a differentially methylated region in the ankyrin 1 (ANK1) gene that is associated with neuropathology in the entorhinal cortex, a primary site of AD manifestation. This region was confirmed as significantly 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, nor 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 the first epigenome-wide association study (EWAS) 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. |
| Databáze: | OpenAIRE |
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