Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
16 08 2023
16 08 2023
Historique:
received:
09
02
2023
accepted:
23
06
2023
medline:
18
8
2023
pubmed:
17
8
2023
entrez:
16
8
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37587191
doi: 10.1038/s42003-023-05070-z
pii: 10.1038/s42003-023-05070-z
pmc: PMC10432557
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
780Subventions
Organisme : NICHD NIH HHS
ID : R01 HD089511
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD094842
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA233774
Pays : United States
Organisme : Medical Research Council
ID : MR/N024524/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N022556/1
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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