학술논문
Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function
Document Type
article
Author
Sally Mortlock; Sahar Houshdaran; Idit Kosti; Nilufer Rahmioglu; Camran Nezhat; Allison F. Vitonis; Shan V. Andrews; Parker Grosjean; Manish Paranjpe; Andrew W. Horne; Alison Jacoby; Jeannette Lager; Jessica Opoku-Anane; Kim Chi Vo; Evelina Manvelyan; Sushmita Sen; Zhanna Ghukasyan; Frances Collins; Xavier Santamaria; Philippa Saunders; Kord Kober; Allan F. McRae; Kathryn L. Terry; Júlia Vallvé-Juanico; Christian Becker; Peter A. W. Rogers; Juan C. Irwin; Krina Zondervan; Grant W. Montgomery; Stacey Missmer; Marina Sirota; Linda Giudice
Source
Communications Biology, Vol 6, Iss 1, Pp 1-17 (2023)
Subject
Language
English
ISSN
2399-3642
Abstract
Abstract Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease.