The largest genetic study ever conducted on endometriosis has revealed significant overlap in genes associated with nearly a dozen other pain conditions, including migraines.
The findings could open a new chapter for research on the underlying causes of the disease and potential new treatments.
Endometriosis, or endo for short, is a highly common, inflammatory condition in which tissue similar to the lining of the uterus grows outside the organ. It's the leading cause of chronic pelvic pain, although symptoms can also include gastrointestinal issues, urinary issues, and persistent fatigue.
What causes the life-altering disease is more or less a mystery, although initial research suggests there's a strong genetic component. Between 30 and 50 percent of endo cases seem to be inheritable, and yet very few genetic risk factors have been identified to date.
Currently, there have been only 9 genome-wide association studies of endometriosis in populations of European and East Asian ancestry, and together, that data identifies about 19 genetic regions associated with the disease.
A meta-analysis, led by the University of Queensland (UQ) in Australia and the University of Oxford, has now more than doubled that number, bringing the suspect list to 42.
The study compared the genomes of 60,000 women with endometriosis and 700,000 women without the disease. The next largest study on the subject considered only 17,000 cases of endo.
"Very little is known about the causes of endometriosis, but studying genetics can give us clues to the biological processes that are the basis for onset and progression," says molecular bioscientist Sally Mortlock from UQ.
In previous genetic studies, for instance, scientists have tied endo risk factors to other conditions with shared symptoms, like depression and gastrointestinal disorders.
The current research once again draws parallels between specific genetic regions that are asspciated with endo and other conditions that involve pain and inflammation, such as migraine, chronic back pain, asthma, and osteoarthritis.
According to Mortlock, these findings should allow future researchers to hone in on what the genes in these specific regions really do. That knowledge could then help experts develop drug targets for new endo treatments.
For instance, the genetic overlap between endo and other pain conditions could imply that the nervous system in some cases has become overly sensitized to pain.
"This makes people suffering from chronic pain more prone to other types of pain," explains Mortlock.
"Perhaps in some cases, we need to be designing pain treatments rather than hormonal treatments."
That said, many of the genes causally linked with endometriosis risk are already known to play a role in signaling processes related to sex-hormones. Others are related to the development of tumors.
In 2022, another study authored by Mortlock also found a genetic link between endometriosis and some types of ovarian cancer.
The connection could help explain why those with endo are slightly more likely to develop ovarian cancers later in life, possibly leading to better treatments for both conditions. The ovaries in particular seem to be tied to extensive endo lesions and scarring.
Ovarian endometriosis in the current study tended to coincide with more extensive endo cases that, in turn, had a stronger genetic basis.
"These results provide support to the hypothesis that the presence of endometriosis can result in pain through interlinked activation of hormonal, immune, and neuronal pathways as is seen in other chronic pain conditions," the authors of the study write.
Most past research on endometriosis has only considered women of reproductive age, who are the cohort most often impacted by the disease. Given the current research was a meta-analysis, its scope was narrowed by previous assumptions.
In reality, endo can also impact women who are no longer menstruating, as well as people who don't identify as women, and, on rare occasions, people assigned male at birth.
Amending this outdated and gendered outlook may reveal even more about the disease, as well as improve diagnosis for everyone.
Currently, the average woman can easily wait up to seven years for an endo diagnosis, and people who don't identify as women often report having their symptoms disregarded or ignored as a result.
The truth is that many doctors today don't feel they have enough information to identify endo or treat it.
Symptoms of the disease are numerous, often subjectively measured, and highly varied from person to person. The only way to tell if someone has endo for certain is through surgery.
Even once that diagnosis has been made, finding helpful treatments that alleviate symptoms without causing side effects or scar tissue is an ongoing challenge for many patients.
Surgery and hormonal therapy are the most common treatments on offer today, yet they don't work the same for everyone. Some researchers suspect that is because endo encompasses a whole variety of subtypes that may require different treatment approaches.
If that's true, future genetic research will be crucial in teasing apart the various ways in which endometriosis can arise and what best to do about it.
The study was published in Nature Genetics.