Largest-Ever Genetic Study of Endometriosis Uncovers 80 Risk Regions

Yale investigators, in collaboration with a team of international scientists, have nearly doubled the known genetic landscape of endometriosis, a chronic and often debilitating inflammatory disease affecting approximately 10% of women worldwide.

By analyzing the genomes of more than 1.4 million women, including over 105,000 cases, the study identifies 80 genomic regions linked to endometriosis risk, 37 of which are new discoveries. This large multi-ancestry study provides the most complete map so far of the biological mechanisms behind the disease.

The research team’s findings were published in Nature Genetics. “This research was a collaborative effort involving investigators with diverse expertise to translate the discovery power of several major biobanks into actionable findings that can improve the care of women affected by endometriosis,” said Renato Polimanti, PhD, MSc, senior author and associate professor of psychiatry at Yale School of Medicine.

Breaking the "Diagnostic Delay" with Genetics

Endometriosis, characterized by endometrial-like tissue growing outside the uterus, often presents with complex symptoms and a diagnostic delay that can last up to a decade. The Yale study explores the genetic links between the disease and its diverse symptoms, such as chronic pelvic pain, migraine, and nausea.

"This study advances our understanding of genetic risk factors for endometriosis and provides molecular support for several leading hypotheses on its pathogenesis," said Dora Koller, PhD, lead author, research affiliate at Yale School of Medicine, and principal investigator at the Women and Perinatal Health Research Group at the Sant Pau Research Institute in Barcelona, Spain.

Key Findings Include:

• Targeted Drug Repurposing: The researchers identified potential new treatments by looking at drugs already FDA-approved for other conditions. Highlights include medications used for breast cancer, contraception, and the prevention of preterm birth.

• Genetic Overlap with Adenomyosis: The study found five genetic loci shared between endometriosis and adenomyosis (a condition where tissue grows into the uterine wall), helping to clarify whether these are distinct diseases or different versions of the same process.

• Global Ancestry Insights: By including participants from diverse population groups, the team demonstrated that while the core biology of the disease is shared globally, specific genetic variations may contribute to how the disease manifests in different regions.

A Path Toward Personalized Care

The integration of "multi-omics" data-combining genetics with protein and tissue analysis-allowed the team to link risk factors to pathways involved in inflammation, hormonal regulation, and tissue remodeling. These insights align with major theories of the disease, including "benign metastasis" and immune dysfunction.

While a genetic test for endometriosis is not yet available for clinical use, the development of these ancestry-informed risk models marks a significant step toward personalized medicine for millions of women suffering in silence.