|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||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|
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.