Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function

Sally Mortlock, Sahar Houshdaran, Idit Kosti, Nilüfer Rahmioğlu, 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 Santamaría, Philippa T. K. Saunders, Kord M. Kober, Allan F. McRae, Kathryn L. Terry, Júlia Vallvé-Juanico, Christian M. Becker, Peter A. W. Rogers, Juan C. Irwin, Krina T. Zondervan, Grant W. Montgomery, Stacey A. Missmer, Marina Sirota, Linda C. Giudice

Communications Biology · 2023

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Summary

This multi-centre study characterised genome-wide DNA methylation patterns in endometrial tissue from nearly 1,000 deeply-phenotyped women to understand epigenetic mechanisms underlying endometriosis and endometrial physiology. The work identified significant methylation differences associated with disease stage, clinical sub-phenotypes, and menstrual cycle phase, and discovered 51 methylation quantitative trait loci linked to endometriosis risk. The findings provide functional epigenetic evidence for candidate genes contributing to endometriosis pathogenesis and a valuable resource for understanding tissue-specific methylation effects on endometrial biology.

Regional applicability

These findings on epigenetic mechanisms of endometriosis are relevant to UK clinical and research contexts, where endometriosis affects approximately 1.5 million women. The identified methylation patterns and genetic variants may inform future diagnostic and therapeutic strategies in UK healthcare settings, though translation to clinical practice would require further validation.

Key measures

DNA methylation profiles; menstrual cycle phase; endometriosis stage and sub-phenotypes; methylation quantitative trait loci (mQTLs); proportion of endometriosis variation explained by DNAm (15.4%); number of mQTLs associated with disease risk

Outcomes reported

The study characterised DNA methylation variation in endometrial samples from 984 participants and identified associations with menstrual cycle phase, endometriosis stage, and genetic variants. It quantified that 15.4% of endometriosis variation is captured by DNA methylation and identified 118,185 independent cis-methylation quantitative trait loci, including 51 associated with endometriosis risk.

Theme
Nutrition & health
Subject
Dietary patterns & chronic disease
Study type
Research
Study design
Observational cohort
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s42003-023-05070-z
Catalogue ID
SNmoj7ntfg-oe3sjj

Topic tags

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