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Alzheimer's disease: Early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci

De Jager, PL and Srivastava, G and Lunnon, K and Burgess, J and Schalkwyk, LC and Yu, L and Eaton, ML and Keenan, BT and Ernst, J and McCabe, C and Tang, A and Raj, T and Replogle, J and Brodeur, W and Gabriel, S and Chai, HS and Younkin, C and Younkin, SG and Zou, F and Szyf, M and Epstein, CB and Schneider, JA and Bernstein, BE and Meissner, A and Ertekin-Taner, N and Chibnik, LB and Kellis, M and Mill, J and Bennett, DA (2014) 'Alzheimer's disease: Early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci.' Nature Neuroscience, 17 (9). 1156 - 1163. ISSN 1097-6256

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Abstract

© 2014 Nature America, Inc. All rights reserved. We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network.

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 13:40
Last Modified: 15 Nov 2018 18:29
URI: http://repository.essex.ac.uk/id/eprint/11016

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