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Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology

Smith, RG and Hannon, E and De Jager, PL and Chibnik, L and Lott, SJ and Condliffe, D and Smith, AR and Haroutunian, V and Troakes, C and Al-Sarraj, S and Bennett, DA and Powell, J and Lovestone, S and Schalkwyk, L and Mill, J and Lunnon, K (2018) 'Elevated DNA methylation across a 48-kb region spanning the HOXA gene cluster is associated with Alzheimer's disease neuropathology.' Alzheimer's and Dementia. ISSN 1552-5260

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Abstract

Introduction Alzheimer's disease is a neurodegenerative disorder that is hypothesized to involve epigenetic dysregulation of gene expression in the brain. Methods We performed an epigenome-wide association study to identify differential DNA methylation associated with neuropathology in prefrontal cortex and superior temporal gyrus samples from 147 individuals, replicating our findings in two independent data sets (N = 117 and 740). Results We identify elevated DNA methylation associated with neuropathology across a 48-kb region spanning 208 CpG sites within the HOXA gene cluster. A meta-analysis of the top-ranked probe within the HOXA3 gene (cg22962123) highlighted significant hypermethylation across all three cohorts (P = 3.11 × 10−18). Discussion We present robust evidence for elevated DNA methylation associated with Alzheimer's disease neuropathology spanning the HOXA gene cluster on chromosome 7. These data add to the growing evidence highlighting a role for epigenetic variation in Alzheimer's disease, implicating the HOX gene family as a target for future investigation.

Item Type: Article
Uncontrolled Keywords: Alzheimer's disease (AD), Braak stage, DNA methylation, Epigenetics, Epigenome-wide association study (EWAS), HOXA, Illumina Infinium 450K BeadChip (450K array), Meta-analysis, Neuropathology, Prefrontal cortex (PFC), Superior temporal gyrus (STG)
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Elements
Date Deposited: 16 Mar 2018 14:12
Last Modified: 20 Mar 2018 15:15
URI: http://repository.essex.ac.uk/id/eprint/21714

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