A study in 1.4 million women expands knowledge on endometriosis and its biological complexity
Endometriosis, a chronic inflammatory disease that affects approximately one in 10 women of reproductive age — around 190 million worldwide — remains poorly understood from a biological perspective, which has historically hindered both its accurate diagnosis and the development of effective treatments. Now, an international study published in the journal Nature Genetics provides new data to better understand the genetic basis and mechanisms involved in this condition.
Endometriosis, a chronic inflammatory disease that affects approximately one in 10 women of reproductive age — around 190 million worldwide — remains poorly understood from a biological perspective, which has historically hindered both its accurate diagnosis and the development of effective treatments. Now, an international study published in the journal Nature Genetics provides new data to better understand the genetic basis and mechanisms involved in this condition.
The study, which analyses genetic information from nearly 1.4 million women, including more than 100,000 cases of endometriosis, constitutes the largest study conducted to date on this disease. It was led by experts from the University of Barcelona, the Sant Pau Research Institute (IR Sant Pau) and Yale University (United States), among other centers in Europe and the United States. The results have identified 80 regions of the genome associated with the risk of developing endometriosis, 37 of which had not been previously described, representing a significant advance in understanding its genetic architecture.
This international study also involves the participation of experts Bru Cormand, Marina Mitjans, and Selena Aranda, from the Department of Genetics, Microbiology and Statistics of the UB’s Faculty of Biology and the Institute of Biomedicine (IBUB), the Sant Joan de Déu Research Institute (IRSJD), and the CIBER Area for Mental Health (CIBERSAM) the Area for Rare Diseases (CIBERER).
“When we study a disease, we need to understand its biological basis. If we do not know what happens at the molecular level, it is very difficult to develop effective treatments or improve diagnosis,” says Dora Koller, lead author of the study and member of the Perinatal and Women’s Health research group at IR Sant Pau and the UB’s Department of Genetics, Microbiology and Statistics. She adds: “Basic research in endometriosis has arrived later than in other areas, which has limited understanding of the disease for years.”
As Professor Bru Cormand details, “this study substantially expands the genetic map of endometriosis and allows us to identify new regions of the genome involved in the risk of developing the disease. These results are important because they help us to better understand the biological mechanisms underlying a highly complex and still little-known pathology.”
“This study leverages a multidisciplinary collaboration to improve endometriosis care. We are dedicated to translating our findings into actionable solutions for women worldwide,” says Renato Polimanti, senior author and Associate Professor of Psychiatry at the Yale School of Medicine.
An integrative approach to understanding disease
The researchers did not limit themselves to identifying statistical associations typical of genome-wide studies, but integrated genetic data with multiple layers of functional information to understand how these variants influence the expression of genes and proteins, and epigenetic processes. This approach has made it possible to go beyond the simple identification of genetic risk and to connect these associations with real biological processes, providing a more comprehensive and mechanistic view of the pathophysiology of endometriosis.
The disease does not respond to a single mechanism, but to the interaction of multiple biological processes acting simultaneously and contributing both to its onset and progression. “What we see is that there is probably not a single cause, but many possible pathways that can contribute to the disease, and these likely vary between women,” notes Koller. “This finding reinforces the idea that endometriosis should be understood as a complex and systemic disease in which multiple interrelated biological mechanisms are involved,” she continues.
A heterogeneous disease with poorly defined subtypes
This biological complexity is reflected in the wide clinical variability of the disease. Some women have hardly any symptoms, while others experience severe and disabling pain or infertility problems that significantly affect their quality of life.
In clinical practice, current classification is mainly based on surgical criteria or the location of lesions, which is limited, as it does not adequately explain differences in symptoms, progression, or response to treatment. This lack of more precise diagnostic tools also contributes to the fact that diagnosis of the disease is often delayed for an average of 7-10 years, even in women with evident symptoms.
Therefore, a shift in the approach would not only improve the understanding of the disease, but also allow diagnosis and treatment to be adapted to the specific characteristics of each patient, a key step towards more personalized medicine.
The combined role of genetics and environmental factors
The study shows that genetic predisposition alone does not explain the development of the disease. Factors such as diet, exposure to certain chemical compounds and many others can modulate its development and progression.
As Marina Mitjans, a Ramón y Cajal researcher, and Selena Aranda point out, “the results show that endometriosis cannot be explained solely by genetic predisposition. The interaction between genetic, environmental and epigenetic factors is key to understanding why the disease appears and evolves differently in each woman.”
Moreover, the analysis of polygenic risk combined with clinical information provides a particularly relevant result: in some cases, symptoms and comorbidities may play a more decisive role than genetics itself in identifying the disease. This finding challenges the idea that genetic risk is always the main indicator and reinforces the importance of a comprehensive clinical evaluation.
New opportunities for diagnosis and personalized treatment
The study also identifies potential new therapeutic options through the repurposing of existing drugs, a strategy that allows accelerating the application of new treatments for endometriosis by building on medications with already known safety profiles. These include drugs used in oncology and others such as nortriptyline, which could have a dual effect by acting on both chronic pain and depression, two conditions frequently associated with the disease.
Reference article:
Koller, Dora et al. “Multi-ancestry genome-wide association and integrated multi-omics analyses of endometriosis and its clinical manifestations”. Nature Genetics, Apriol 2026. DOI: 10.1038/s41588-026-02582-2
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Dora Koller, , lead author of the study and member of the UB’s Department of Genetics, Microbiology and Statistics and the Perinatal and Women’s Health research group at IR Sant Pau.
