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

Alzheimers Dement

Authors	Rebecca Smith Eilis Hannon Philip De Jager Lori Chibnik Simon Lott Daniel Condliffe Adam Smith Vahram Haroutunian Claire Troakes Safa Al-Sarraj David Bennett John Powell Simon Lovestone Leonard Schalkwyk Jonathan Mill Katie Lunnon
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.
Year of Publication	2018
Journal	Alzheimers Dement
Volume	14
Issue	12
Pages	1580-1588
Date Published	2018 Dec
ISSN	1552-5279
DOI	10.1016/j.jalz.2018.01.017
PubMed ID	29550519
PubMed Central ID	PMC6438205
Links
Grant list	RF1 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