Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function.
Sally MortlockSahar HoushdaranIdit KostiNilufer RahmiogluCamran NezhatAllison F VitonisShan V AndrewsParker GrosjeanManish ParanjpeAndrew W HorneAlison JacobyJeannette LagerJessica Opoku-AnaneKim Chi VoEvelina ManvelyanSushmita SenZhanna GhukasyanFrances CollinsXavier SantamariaPhilippa T K SaundersKord M KoberAllan F McRaeKathryn L TerryJúlia Vallvé-JuanicoChristian M BeckerPeter A W RogersJuan C IrwinKrina T ZondervanGrant W MontgomeryStacey MissmerMarina SirotaLinda C GiudicePublished in: Communications biology (2023)
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.
Keyphrases
- dna methylation
- genome wide
- gene expression
- endometrial cancer
- public health
- mental health
- polycystic ovary syndrome
- healthcare
- type diabetes
- chronic pain
- high resolution
- metabolic syndrome
- electronic health record
- adipose tissue
- insulin resistance
- health information
- skeletal muscle
- big data
- neuropathic pain
- mass spectrometry
- postoperative pain