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Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles by Walker, Rosie M. ;Vaher, Kadi ;Bermingham, Mairead L. ;Morris, Stewart W. ;Bretherick, Andrew D. ;Zeng, Yanni ;Rawlik, Konrad ;Amador, Carmen ;Campbell, Archie ;Haley, Chris S. ;Hayward, Caroline ;Porteous, David J. ;McIntosh, Andrew M. ;Marioni, Riccardo E. ;Evans, Kathryn L. is a scholarly article available to read on EtoBox.

What is Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles about?

## Abstract ## Background The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease, whilst the ε2 allele confers protection. Previous studies report differential DNA methylation of APOE between ε4 and ε2 carriers, but associations with epigenome-wide methylation have not previously been characterised. ## Methods Using the EPIC array, we investigated epigenome-wide differences in whole blood DNA methylation patterns between Alzheimer’s disease-free APOE ε4 (n = 2469) and ε2 (n = 1118) carriers from the two largest single-cohort DNA methylation samples profiled to date. Using a discovery, replication and meta-analysis study design, methylation differences were identified using epigenome-wide association analysis and differentially methylated region (DMR) approaches. Results were explored using pathway and methylation quantitative trait loci (meQTL) analyses. ## Results We obtained replicated evidence for DNA methylation differences in a ~ 169 kb region, which encompasses part of APOE and several upstream genes. Meta-analytic approaches identified DNA methylation differences outside of APOE: differentially methylated positions were

Author

Walker, Rosie M. ;Vaher, Kadi ;Bermingham, Mairead L. ;Morris, Stewart W. ;Bretherick, Andrew D. ;Zeng, Yanni ;Rawlik, Konrad ;Amador, Carmen ;Campbell, Archie ;Haley, Chris S. ;Hayward, Caroline ;Porteous, David J. ;McIntosh, Andrew M. ;Marioni, Riccardo E. ;Evans, Kathryn L.

Publisher

Springer Science and Business Media LLC

Published

2021

Language

EN