Sistema de Salut de Catalunya
Institut Català de la Salut
[Mortlock S] The Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. [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. [Santamaria X] Carlos Simon Foundation, Health Research Institute, Valencia, Spain. Grup de Recerca Biomèdica en Ginecologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-09-20T08:48:19Z
2023-09-20T08:48:19Z
2023-08-16
Epigenomics; Genetic predisposition to disease; Urogenital reproductive disorders
Epigenómica; Predisposición genética a la enfermedad; Trastornos reproductivos urogenitales
Epigenòmica; Predisposició genètica a la malaltia; Trastorns reproductius urogenitals
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.
This work has been supported by the National Institutes of Health (NIH) NICHD R01 HD089511. It was also supported, in part, by funding from Wellbeing of Women (through sponsorship from PwC) (R42533) and the Medical Research Council (MR/N024524/1 and MR/N022556/1) and NIH HD094842 (Harvard/MSU). K.K. was supported by NIH NCI R37 CA233774. A.F.M. was supported by an Australian Research Council Future Fellowship (FT200100837). G.W.M. was supported by NHMRC Fellowship (GNT1177194).
Article
Published version
English
Endometriosi - Aspectes genètics; ADN - Metilació; PHENOMENA AND PROCESSES::Chemical Phenomena::Biochemical Phenomena::Alkylation::Methylation::DNA Methylation; DISEASES::Female Urogenital Diseases and Pregnancy Complications::Female Urogenital Diseases::Genital Diseases, Female::Endometriosis; Other subheadings::Other subheadings::Other subheadings::/genetics; FENÓMENOS Y PROCESOS::fenómenos químicos::fenómenos bioquímicos::alquilación::metilación::metilación del ADN; ENFERMEDADES::enfermedades de los genitales femeninos y complicaciones del embarazo::enfermedades urogenitales femeninas::enfermedades de los genitales femeninos::endometriosis; Otros calificadores::Otros calificadores::Otros calificadores::/genética
Nature Portfolio
Communications Biology;6
https://doi.org/10.1038/s42003-023-05070-z
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
Articles científics - VHIR [1655]
