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| EWAS ID | EWAS400 |
| GSE ID | GSE59685 |
| EWAS Title | Cross-tissue methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer’s disease neuropathology |
| Disease/Phenotype | Alzheimer's disease |
| Group1 | source tissue: superior temporal gyrus |
| Group2 | source tissue: frontal cortex |
| Group1 Sample Size | 117 |
| Group2 Sample Size | 114 |
| Summary | 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 three 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. |
| Contributor | Lunnon K, Smith R, Hannon E, De Jager PL, Srivastava G, Volta M, Troakes C, Al-Sarraj S, Burrage J, Macdonald R, Condliffe D, Harries LW, Katsel P, Haroutunian V, Kaminsky Z, Joachim C, Powell J, Lovestone S, Bennett DA, Schalkwyk LC, Mill J |
| Public date | Public on Aug 17, 2014 |
| Citation (PubMed ID) | 25129077 |
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