In a recent study, published in Nature, researchers conducted a large genome-wide association study on endometriosis, including data from more than 60,000 women. The study identified 42 genome-wide significant loci comprising of 49 distinct association signals, as well as other findings which could aid the development of better-targeted treatments and non-invasive diagnostic methods for endometriosis.
Understanding the genetic basis of endometriosis
Endometriosis is a common and debilitating condition which affects 5-10% of women of reproductive age, characterized by the presence of endometrial-like tissue outside the uterus, mainly on pelvic organs. Symptoms of endometriosis include severe pelvic pain and infertility, and the global average for delay in diagnosis is 7 years from symptom onset. Currently, treatments are limited to surgical removal of disease and adhesions or hormonal treatments that can have problematic side effects.
Endometriosis is a heterogeneous condition that is typically classified based on the extent and severity of the disease. However, the presence of deep endometriosis, which can infiltrate bowel, ureter, bladder, and rectovaginal lesions, is not accounted for in the current classification system. The causes of endometriosis remain largely unknown, although the condition has an estimated heritability of approximately 50%, with common genetic variation accounting for 26% of cases. Nine genome-wide association studies have been conducted previously, identifying 19 distinct associations of genome-wide significance that map to 13 loci, explaining 1.75% of the phenotypic variance for endometriosis.
The findings of the study
This study was a genome-wide association study meta-analysis conducted by 25 global centres, including data from 60,674 cases and 701,926 controls of European and East Asian descent. This makes it one of the largest GWAS meta-analyses of endometriosis to date. The researchers identified 42 genome-wide significant loci comprising of 49 distinct association signals. This represents a threefold increase from previous studies, with identified signals explaining up to 5.01% of disease variance. The study also revealed that ovarian endometriosis has a different genetic basis than superficial peritoneal disease.
The study analysed the association between these risk variants, gene expression and DNA methylation patterns in the endometrium and blood. The study also found shared genetic basis between endometriosis and other pain conditions such as migraine, back pain, and multi-site pain. The study highlights the genes implicated in pain mechanisms, suggesting that genetics may contribute to the sensitisation of the central nervous system that some chronic pain patients experience.
Implications and future directions
The study provides a plethora of new results, with the hope that this will aid the development of new treatments better targeted to subtypes of endometriosis and its symptoms, as well as the development of non-invasive diagnostic methods. The findings provide important insights into the mechanisms of endometriosis and its association with sub-phenotypes, facilitating early symptomatic intervention and aiding the development of new treatments.
This study is especially significant for women’s health, which has often been neglected in research and healthcare. Endometriosis, in particular, has not been taken seriously in the past, with many women being dismissed or misdiagnosed by healthcare professionals. This study represents a shift in attitudes towards endometriosis, recognizing it as a serious and debilitating condition that requires more research and attention. By understanding the genetic basis of endometriosis, we can work towards developing more effective treatments and improving the quality of life for millions of women worldwide.
