A large genomic study published in Nature Genetics identified 80 genetic regions associated with endometriosis risk, including 37 newly reported loci, providing additional insight into the molecular mechanisms underlying the disease.
The investigators analyzed genetic data from approximately 1.4 million women, including more than 105,000 patients with endometriosis or adenomyosis, using data from multiple international biobanks and research cohorts. The study included multi-ancestry participants from European, East Asian, African, and American populations to evaluate disease-associated genetic variation across ancestries.
Endometriosis affects approximately 10 percent of women and is commonly associated with chronic pelvic pain, infertility, fatigue, and gastrointestinal symptoms. Diagnosis is often delayed because symptoms overlap with other disorders, and definitive diagnosis may still require laparoscopic evaluation.
The study identified 80 genomic regions linked to endometriosis susceptibility, with five also associated with adenomyosis. Integrated transcriptomic, epigenetic, proteomic, and single-cell analyses linked these variants to pathways involved in immune regulation, inflammation, hormone signaling, angiogenesis, tissue remodeling, and cellular differentiation.
Several implicated genes were also associated with chronic pain signaling and reproductive system function, supporting the concept that endometriosis may involve systemic biological processes in addition to localized pelvic disease. The investigators further reported associations between polygenic risk scores and symptoms including abdominal pain, migraine, anxiety, and nausea.
The findings may help support future development of biomarker-based diagnostic approaches. Noninvasive laboratory testing for endometriosis remains limited, and current diagnosis still relies heavily on clinical assessment and surgical confirmation. The identification of disease-associated genetic and molecular pathways may help guide future genomic, transcriptomic, or proteomic assays aimed at earlier detection and disease stratification.
The researchers also performed drug-repurposing analyses that highlighted pathways linked to medications currently used in breast cancer treatment, hormonal contraception, and preterm birth prevention. The authors emphasized that these findings remain exploratory and require additional validation before clinical application.
The study authors noted several limitations, including the use of both self-reported and clinically diagnosed cases in some datasets and the predominance of European ancestry participants despite the multi-ancestry design. They stated that further studies integrating molecular profiling with clinical phenotyping may improve understanding of endometriosis subtypes and support future precision diagnostic strategies.
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