An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene

Janou A. Y. Roubroeks, Adam R. Smith, Rebecca G. Smith, Ehsan Pishva, Zina Ibrahim, Martina Sattlecker, Eilis J. Hannon, Iwona Kloszewska, Patrizia Mecocci, Hilkka Soininen, Magda Tsolaki, Bruno Vellas, Lars-Olof Wahlund, Dag Aarsland, Petroula Proitsi, Angela Hodges, Simon Lovestone, Stephen J. Newhouse, Richard J. B. Dobson, Jonathan MillDaniel L. A. van den Hove, Katie Lunnon*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Web of Science)

Abstract

A growing number of epigenome-wide association studies have demonstrated a role for DNA methylation in the brain in Alzheimer's disease. With the aim of exploring peripheral biomarker potential, we have examined DNA methylation patterns in whole blood collected from 284 individuals in the Add-NeuroMed study, which included 89 nondemented controls, 86 patients with Alzheimer's disease, and 109 individuals with mild cognitive impairment, including 38 individuals who progressed to Alzheimer's disease within 1 year. We identified significant differentially methylated regions, including 12 adjacent hypermethylated probes in the HOXB6 gene in Alzheimer's disease, which we validated using pyrosequencing. Using weighted gene correlation network analysis, we identified comethylated modules of genes that were associated with key variables such as APOE genotype and diagnosis. In summary, this study represents the first large-scale epigenome-wide association study of Alzheimer's disease and mild cognitive impairment using blood. We highlight the differences in various loci and pathways in early disease, suggesting that these patterns relate to cognitive decline at an early stage. (C) 2020 The Authors. Published by Elsevier Inc.

Original languageEnglish
Pages (from-to)26-45
Number of pages20
JournalNeurobiology of Aging
Volume95
DOIs
Publication statusPublished - Nov 2020

Keywords

  • ALGORITHM
  • Alzheimer's disease (AD)
  • BIOMARKERS
  • Biomarker
  • Blood
  • DEMENTIA
  • DISCOVERY
  • DNA methylation
  • HOXB6
  • MESSENGER-RNA EXPRESSION
  • METHYLATION
  • MILD COGNITIVE IMPAIRMENT
  • Mild cognitive impairment (MCI)
  • OXYTOCIN
  • PACKAGE
  • PATTERN
  • RISK

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