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

Lunnon, K and Smith, R and Hannon, E and De Jager, PL and Srivastava, G and Volta, M and Troakes, C and Al-Sarraj, S and Burrage, J and Macdonald, R and Condliffe, D and Harries, LW and Katsel, P and Haroutunian, V and Kaminsky, Z and Joachim, C and Powell, J and Lovestone, S and Bennett, DA and Schalkwyk, LC and Mill, J (2014) 'Methylomic profiling implicates cortical deregulation of ANK1 in Alzheimer's disease.' Nature Neuroscience. ISSN 1097-6256 (In Press)

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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 a nd highlights the power of this approach for identifying methylomic variation associated with complex disease.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 24 Oct 2014 13:47
Last Modified: 17 Aug 2017 17:46
URI: http://repository.essex.ac.uk/id/eprint/11059

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