A team of researchers from the Yale School of Medicine conducted a genome-wide association study (GWAS) of endometriosis and adenomyosis, the results of which were published in the peer-reviewed scientific journal Nature. The study analyzed genetic data from approximately 1.4 million women, including 105,869 confirmed cases of endometriosis. The research aimed to expand the identification of genetic loci associated with endometriosis across diverse ethnic populations, evaluate symptom-specific genetic effects, and perform an integrated analysis of multi-omic data. This study represents one of the largest and most comprehensive investigations into the genetic etiology of endometriosis to date.
Endometriosis is a chronic, progressive, and systemic inflammatory disease in which tissue similar to the lining of the uterus grows outside the uterus—on the ovaries, fallopian tubes, and other pelvic organs. This condition is associated with severe menstrual and chronic pelvic pain, dyspareunia (persistent or recurrent pain during sexual intercourse), abdominal bloating, fatigue, anxiety, depression, and infertility. The disease affects approximately 10% of reproductive-age women worldwide, or about 190 million people. Adenomyosis is a pathological condition in which the lining of the uterus (endometrium) grows into the muscular wall of the uterus (myometrium). The condition can involve the entire uterus or be localized in specific parts. Despite the high prevalence of these diseases, their pathogenesis remains incompletely understood.
The researchers identified 80 genomic regions associated with the risk of developing endometriosis, 37 of which were previously unknown. Five of the identified loci were found to be associated with both endometriosis and adenomyosis simultaneously. Furthermore, putative causal genetic variants were identified, underlying more than 50 of these associations.
Transcriptomic, epigenetic, and proteomic analyses revealed that the genetic risk for endometriosis is linked to biological processes such as cellular differentiation, immune and hormonal regulation, tissue remodeling, and inflammatory processes. These findings align with existing hypotheses on the development of endometriosis, including immune dysfunction and the theory of so-called “benign metastasis.”
A priority focus of the study was drug-repurposing analysis. The researchers identified several FDA-approved therapeutic agents currently used for the treatment of breast cancer, hormonal contraception, and the prevention of preterm birth, which may be considered for the treatment of endometriosis.
The inclusion of diverse population groups in the study showed that, despite shared pathophysiological mechanisms, specific genetic variations may account for different clinical manifestations of the disease. While genetic testing for endometriosis is not yet available in clinical practice, the development of these genetic risk models represents a significant step forward for personalized medicine. This innovation will eventually contribute to earlier diagnosis, individual risk assessment, and the development of effective, patient-tailored therapeutic strategies.
Sources: technologynetworks.com
