RT Journal Article
SR Electronic
T1 Assessment of DNA methylation differences between carriers of <em>APOE</em> ε4 and <em>APOE</em> ε2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 815035
DO 10.1101/815035
A1 Rosie M. Walker
A1 Kadi Vaher
A1 Mairead L. Bermingham
A1 Stewart W. Morris
A1 Andrew D. Bretherick
A1 Yanni Zeng
A1 Konrad Rawlik
A1 Carmen Amador
A1 Archie Campbell
A1 Chris S. Haley
A1 Caroline Hayward
A1 David J. Porteous
A1 Andrew M. McIntosh
A1 Riccardo E. Marioni
A1 Kathryn L. Evans
YR 2019
UL http://biorxiv.org/content/early/2019/10/23/815035.abstract
AB INTRODUCTION The Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD), while the ε2 allele confers protection. Previous studies report differential DNA methylation of APOE between ε4 and ε2 carriers but associations with epigenome-wide methylation are unknown.METHODS The EPIC array was used to identify methylation differences between AD-free APOE ε4 (n=2469) and ε2 (n=1108) carriers using epigenome-wide association analysis and differentially methylated region (DMR) approaches. Results were explored using pathway and meQTL analyses.RESULTS Differentially methylated positions were identified in APOE, surrounding genes and genes outside of this locus (DHCR24, LDLR and ABCG1). DMRs were identified in SREBF2, LDLR and SQLE. Pathway and meQTL analyses implicated lipid-related processes; however, blood cholesterol levels could not fully account for the associations.DISCUSSION APOE ε4 vs. ε2 carrier status is associated with epigenome-wide methylation differences in cis and trans in genes involved in lipid homeostasis.