Identification of Novel Susceptibility Methylation Loci for Pancreatic Cancer in a Two-Phase Epigenome-Wide Association Study

Authors

Ziqiao Wang
Yue Lu
Myriam Fornage
Li Jiao
Jianjun Shen
Donghui Li
Peng Wei

Publication Date

11-1-2022

Journal

Epigenetics

Abstract

The role of DNA methylation and its interplay with gene expression in the susceptibility to pancreatic cancer (PanC) remains largely unexplored. To fill in this gap, we conducted an integrative two-phase epigenome-wide association study (EWAS) of PanC using genomic DNA from 44 cases and 556 controls (20 local controls and 536 public controls in the Framingham Heart Study) in phase 1 and 23 cases and 22 controls in phase 2. We validated the findings using pre-diagnostic blood samples from 13 cases and 26 controls in the Women's Health Initiative (WHI) Study. We further examined gene expression in peripheral leukocytes of 47 cases and 31 controls involved in the methylation study using RNA sequencing and performed bidirectional Mendelian randomization (MR) analysis using existing single nucleotide polymorphism (SNP) data. In phase 1, we identified 2776 significantly differentially methylated CpG sites (DMPs) and 154 significantly differentially methylated regions (DMRs). In phase 2, we validated six DMPs (in or near

Keywords

Humans, Female, Epigenome, DNA Methylation, Genome-Wide Association Study, DNA, Pancreatic Neoplasms, CpG Islands, Epigenesis, Genetic

Comments

Associated Data

PMID: 35030986