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Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease.
|Publication Type||Journal Article|
|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, and Mill J.|
|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.|
|Year of Publication||2014|
|Date Published (YYYY/MM/DD)||2014/09/01|