Communications Biology (Aug 2023)
Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function
- 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
Affiliations
- Sally Mortlock
- The Institute for Molecular Bioscience, The University of Queensland
- Sahar Houshdaran
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Idit Kosti
- Bakar Computational Health Sciences Institute, University of California San Francisco
- Nilufer Rahmioglu
- Wellcome Centre for Human Genetics, University of Oxford
- Camran Nezhat
- Stanford University Medical Center
- Allison F. Vitonis
- Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital and Harvard Medical School
- Shan V. Andrews
- Bakar Computational Health Sciences Institute, University of California San Francisco
- Parker Grosjean
- Bakar Computational Health Sciences Institute, University of California San Francisco
- Manish Paranjpe
- Bakar Computational Health Sciences Institute, University of California San Francisco
- Andrew W. Horne
- MRC Centre for Reproductive Health, University of Edinburgh, QMRI
- Alison Jacoby
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Jeannette Lager
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Jessica Opoku-Anane
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Kim Chi Vo
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Evelina Manvelyan
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Sushmita Sen
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Zhanna Ghukasyan
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Frances Collins
- MRC Centre for Reproductive Health, University of Edinburgh, QMRI
- Xavier Santamaria
- Carlos Simon Foundation, Health Research Institute
- Philippa Saunders
- Centre for Inflammation Research, Institute for Regeneration and Repair University of Edinburgh
- Kord Kober
- Bakar Computational Health Sciences Institute, University of California San Francisco
- Allan F. McRae
- The Institute for Molecular Bioscience, The University of Queensland
- Kathryn L. Terry
- Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital and Harvard Medical School
- Júlia Vallvé-Juanico
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Christian Becker
- Oxford Endometriosis CaRe Centre, Nuffield Department of Women’s and Reproductive Health, John Radcliffe Hospital, University of Oxford
- Peter A. W. Rogers
- University of Melbourne Department of Obstetrics and Gynaecology, Royal Women’s Hospital
- Juan C. Irwin
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- Krina Zondervan
- Wellcome Centre for Human Genetics, University of Oxford
- Grant W. Montgomery
- The Institute for Molecular Bioscience, The University of Queensland
- Stacey Missmer
- Department of Epidemiology, Harvard T.H. Chan School of Public Health
- Marina Sirota
- Bakar Computational Health Sciences Institute, University of California San Francisco
- Linda Giudice
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco
- DOI
- https://doi.org/10.1038/s42003-023-05070-z
- Journal volume & issue
-
Vol. 6,
no. 1
pp. 1 – 17
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.
