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Alzheimers Dement DOI:10.1016/j.jalz.2018.01.017

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

Publication TypeJournal Article
Year of Publication2018
AuthorsSmith, RG, Hannon, E, De Jager, PL, Chibnik, L, Lott, SJ, Condliffe, D, Smith, AR, Haroutunian, V, Troakes, C, Al-Sarraj, S, Bennett, DA, Powell, J, Lovestone, S, Schalkwyk, L, Mill, J, Lunnon, K
JournalAlzheimers Dement
Volume14
Issue12
Pages1580-1588
Date Published2018 Dec
ISSN1552-5279
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).

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.

DOI10.1016/j.jalz.2018.01.017
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29550519?dopt=Abstract

Alternate JournalAlzheimers Dement
PubMed ID29550519
PubMed Central IDPMC6438205
Grant ListRF1 AG036042 / AG / NIA NIH HHS / United States
P50 AG016574 / AG / NIA NIH HHS / United States
K25 AG041906 / AG / NIA NIH HHS / United States
R01 MH064673 / MH / NIMH NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
KL2 RR024151 / RR / NCRR NIH HHS / United States
R01 AG036042 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG032990 / AG / NIA NIH HHS / United States
RC2 AG036547 / AG / NIA NIH HHS / United States
P01 AG002219 / AG / NIA NIH HHS / United States
P50 AG005138 / AG / NIA NIH HHS / United States
MR/L016397/1 / / Medical Research Council / United Kingdom
R01 AG036039 / AG / NIA NIH HHS / United States
U01 ES017155 / ES / NIEHS NIH HHS / United States
R01 AG018023 / AG / NIA NIH HHS / United States
R01 AG036836 / AG / NIA NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States