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

Autor: Mortlock S; The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia. s.mortlock@imb.uq.edu.au., Houshdaran S; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA., Kosti I; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA., Rahmioglu N; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.; Oxford Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, John Radcliffe Hospital, University of Oxford, Oxford, UK., Nezhat C; Stanford University Medical Center, Palo Alto, CA, USA.; University of California San Francisco, San Francisco, CA, USA.; Camran Nezhat Institute, Center for Special Minimally Invasive and Robotic Surgery, Woodside, CA, USA., Vitonis AF; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA., Andrews SV; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA., Grosjean P; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA., Paranjpe M; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA., Horne AW; MRC Centre for Reproductive Health, University of Edinburgh, QMRI, Edinburgh, UK., Jacoby A; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA., Lager J; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA., Opoku-Anane J; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA., Vo KC; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA., Manvelyan E; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA., Sen S; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA., Ghukasyan Z; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA., Collins F; MRC Centre for Reproductive Health, University of Edinburgh, QMRI, Edinburgh, UK., Santamaria X; Carlos Simon Foundation, Health Research Institute, Valencia, Spain.; Group of Biomedical Research in Gynecology, Vall d'Hebron Research Institute, Barcelona, Spain., Saunders P; Centre for Inflammation Research, Institute for Regeneration and Repair University of Edinburgh, Edinburgh, UK., Kober K; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA.; Department of Physiological Nursing, University of California San Francisco, San Francisco, CA, USA., McRae AF; The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Terry KL; Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Boston Center for Endometriosis, Boston Children's Hospital and Brigham and Women's Hospital, Boston, MA, USA., Vallvé-Juanico J; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA.; Group of Biomedical Research in Gynecology, Vall d'Hebron Research Institute, Barcelona, Spain., Becker C; Oxford Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, John Radcliffe Hospital, University of Oxford, Oxford, UK., Rogers PAW; University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Melbourne, Australia., Irwin JC; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA., Zondervan K; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.; Oxford Endometriosis CaRe Centre, Nuffield Department of Women's and Reproductive Health, John Radcliffe Hospital, University of Oxford, Oxford, UK., Montgomery GW; The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia., Missmer S; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.; Boston Center for Endometriosis, Boston Children's Hospital and Brigham and Women's Hospital, Boston, MA, USA.; Division of Adolescent and Young Adult Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.; Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI, USA., Sirota M; Bakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, CA, USA.; Department of Pediatrics, Division of Neonatology, University of California San Francisco, San Francisco, CA, USA., Giudice L; Center for Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, CA, USA. Linda.Giudice@ucsf.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Aug 16; Vol. 6 (1), pp. 780. Date of Electronic Publication: 2023 Aug 16.
DOI: 10.1038/s42003-023-05070-z
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje