RT Journal Article
SR Electronic
T1 Global Endometrial DNA Multi-omics Analysis Reveals Insights into mQTL Regulation and Associated Endometriosis Disease Risk
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.27.518106
DO 10.1101/2022.11.27.518106
A1 Sally Mortlock
A1 Sahar Houshdaran
A1 Idit Kosti
A1 Nilufer Rahmioglu
A1 Camran Nezhat
A1 Allison F. Vitonis
A1 Shan V. Andrews
A1 Parker Grosjean
A1 Manish Paranjpe
A1 Andrew W. Horne
A1 Alison Jacoby
A1 Jeannette Lager
A1 Jessica Opoku-Anane
A1 Kim Chi Vo
A1 Evelina Manvelyan
A1 Sushmita Sen
A1 Zhanna Ghukasyan
A1 Frances Collins
A1 Xavier Santamaria
A1 Philippa Saunders
A1 Kord Kober
A1 Allan F. McRae
A1 Kathryn L. Terry
A1 Júlia Vallvé-Juanico
A1 Christian Becker
A1 Peter A.W. Rogers
A1 Juan C. Irwin
A1 Krina Zondervan
A1 Grant W. Montgomery
A1 Stacey Missmer
A1 Marina Sirota
A1 Linda Giudice
YR 2022
UL http://biorxiv.org/content/early/2022/11/28/2022.11.27.518106.abstract
AB Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Identifying biologic and genetic effects on DNA methylation (DNAm) in endometrium increases understanding of mechanisms that influence gene regulation predisposing to endometriosis and offers an opportunity for novel therapeutic target discovery. Herein, we characterize variation in endometrial DNAm and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genome-wide genotype data and methylation at 759,345 DNAm sites in endometrial samples from 984 deeply-phenotyped participants. We identify significant differences in DNAm profiles between menstrual cycle phases and at four DNAm sites between stage III/IV endometriosis and controls. We estimate that 15.4% of the variation in endometriosis is captured by DNAm, and identify DNAm networks associated with endometriosis. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTL including some tissue-specific effects. We find significant differences in DNAm profiles between endometriosis sub- phenotypes and a significant association between genetic regulation of methylation in endometrium and disease risk, providing functional evidence for genomic targets contributing to endometriosis risk and pathogenesis.Competing Interest StatementThe authors have declared no competing interest.