Genome analysis of approximately 1.4 million women identifies 80 endometriosis-associated regions, including 37 new loci
Expanding the genetic landscape of endometriosis
A genome-wide association study (GWAS) of approximately 1.4 million women identified 80 genomic regions associated with endometriosis risk, including 37 newly reported loci. The researchers combined data from populations with diverse genetic ancestries with analyses at multiple molecular levels to investigate genetic risk and related biological pathways.
Endometriosis is a chronic systemic disease affecting about 10% of women, but its genetic background and molecular mechanisms remain incompletely understood. This study aimed to expand the search for associated loci and examine genetic effects across symptoms. Adenomyosis was also included in the analysis, and the findings were published as a research article in Nature Genetics.
Candidate mechanisms narrowed down using associated loci and multiomics
The analysis included approximately 1.4 million women, among them 105,869 patients. The researchers reported 80 regions associated with endometriosis risk, including 37 new loci, and identified five loci also associated with adenomyosis. Because a locus refers to a specific genomic position or region, the number of loci discovered should not be interpreted directly as the number of risk genes.
The researchers inferred candidate causal variants for more than 50 associations. Among genetic signals associated with disease risk, they narrowed down variants that may be involved in biological effects. Identifying candidates does not mean that experiments have established the causal role of each variant.
An integrated analysis of transcriptomic, epigenomic, and proteomic data from multiple tissues linked endometriosis risk to pathways involving cell differentiation, immune and hormonal regulation, tissue remodeling, and inflammation. Adding molecular-level information to the genetic association findings helped specify pathways for follow-up research. However, the provided abstract does not report tissue-specific results or the effect sizes of individual variants.
The polygenic risk for endometriosis, assessed by combining multiple genetic variants, showed interactions with abdominal pain, anxiety, migraine, and nausea. The abstract does not describe the direction or magnitude of these interactions. These findings are difficult to interpret as evidence that genetic risk directly causes those symptoms, or that symptoms can accurately predict an individual’s risk of developing the disease.
Challenges between treatment-candidate discovery and clinical use
A drug-repurposing analysis identified therapies currently used for breast cancer treatment, contraception, and prevention of preterm birth as potential candidates. This offers leads for reconsidering existing therapies in endometriosis research, but the provided abstract contains no clinical trial results testing their efficacy or safety in patients with endometriosis.
The study expands the map of genetic risk factors and adds molecular evidence to several hypotheses about disease mechanisms. It does not support the conclusion that individualized early diagnosis or preventive intervention is now possible. The functions of candidate causal variants and the potential applicability of treatment candidates remain to be investigated in follow-up research.
The study population and main findings are described in the paper abstract indexed in Europe PMC.
Nature Genetics, Published online: 29 April 2026; doi:10.1038/s41588-026-02582-2 Multi-ancestry genome-wide association analyses coupled with multi-omics integration identify new risk loci for endometriosis and adenomyosis, shed light on underlying molecular mechanisms and suggest potential therapeutic interventions.
This study connects genetic association signals in endometriosis with molecular pathways, providing a basis for prioritizing follow-up experiments. For example, researchers can investigate links between candidate causal variants and immune or hormonal regulatory pathways, then design experiments to test how those variants affect cell function. The drug-repurposing results also offer a starting point for considering which existing therapies warrant further evaluation. Genetic associations and candidate discovery alone, however, cannot justify changing treatment choices for patients. The usefulness of individual risk prediction and the efficacy and safety of candidate therapies require separate validation.