An Epigenome-wide Association Study of Alzheimer's Disease Blood Highlights Robust DNA Hypermethylation in the HOXB6 Gene

Overview

Journal Neurobiol Aging

Publisher Elsevier

Specialties Geriatrics
Neurology
Physiology

Date 2020 Aug 4

PMID 32745807

Citations 28

Authors

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 Mill

Daniel L A van den Hove

Katie Lunnon

Affiliations

Soon will be listed here.

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 AddNeuroMed 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.

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