Scientific Publications

Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease.

Publication TypeJournal Article
AuthorsLunnon, 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.
AbstractAlzheimer'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 Publication2014
JournalNature neuroscience
Volume17
Issue9
Pages1164-1170
Date Published (YYYY/MM/DD)2014/09/01
ISSN Number1097-6256
DOI10.1038/nn.3782
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/25129077?dopt=Abstract