The largest genetic study ever conducted on endometriosis has shown significant overlap in genes associated with a dozen other pain disorders, including migraines.
These findings may open a new chapter in the search for the causes of the disease and new treatment options.
Endometriosis, or endo for short, is a very common, inflammatory disease in which tissue similar to the uterus grows outside of the uterus. It is a common cause of chronic pelvic pain, although symptoms can include stomach problems, urinary problems, and chronic fatigue.
The causes of the life-changing disease are poorly understood, although preliminary research suggests a strong genetic component. Between 30 and 50 percent of endo cases appear to be hereditary, but very few genetic causes have been identified so far.
So far, there have been only 9 genome-wide association studies of endometriosis in people of European and East Asian ancestry, and together, these data show about 19 regions related to the disease.
A meta-analysis, led by the University of Queensland (UQ) in Australia and the University of Oxford, has now doubled this number, bringing the list of suspects to 42.
The study compared the genomes of 60,000 women with endometriosis and 700,000 women without the disease. The next large study on the subject looked at just 17,000 endo cases.
“Very little is known about what causes endometriosis, but studying genetics can give us insight into how the condition develops and how it develops,” says UQ’s Sally Mortlock.
In previous genetic studies, for example, scientists linked risk factors to other conditions with shared symptoms, such as depression and gastrointestinal disorders.
Current research also includes similarities between some of the conditions associated with endo and others that involve pain and inflammation, such as migraine, chronic back pain, asthma, and osteoarthritis.
According to Mortlock, these findings should allow future researchers to determine what the genes in these regions actually do. That knowledge could help scientists develop new endo drug targets.
For example, genetic overlap between endo and other pain disorders may mean that the nervous system is sometimes more sensitive to pain.
“This causes people who suffer from chronic pain to have a different type of pain,” explains Mortlock.
“Maybe in some cases, we need to develop painkillers instead of hormones.”
That said, many of the genes associated with endometriosis risk are already known to be involved in signaling related to sex hormones. Some are related to tumor growth.
In 2022, another study by Mortlock also found a genetic link between endometriosis and other types of ovarian cancer.
The connection may help explain why those with endo are more likely to develop breast cancer later in life, making them more likely to receive better treatment for both conditions. Ovary in particular appears to be attached to endo tumors and lesions.
Ovarian endometriosis in recent studies tended to be associated with many endo conditions that, in turn, had a strong genetic basis.
“These results provide support to the idea that the presence of endometriosis can cause pain due to the connection of hormonal, immune, and neuronal processes as seen in other cases of chronic pain,” the authors wrote.
Most of the previous research on endometriosis focused on women of reproductive age, which is the group most often affected by the disease. Since the current study was a meta-analysis, the number was limited by previous recommendations.
In fact, endo can also affect women who no longer have periods, as well as people who do not identify as female, and, in some cases, people who were assigned male at birth.
Addressing stereotypes and gender stereotypes can reveal more about the disease, and improve everyone’s awareness.
Currently, many women can wait up to seven years to be diagnosed, and people who do not identify as women often report that their symptoms are ignored or ignored.
The truth is that many doctors today do not feel they have enough knowledge to diagnose or treat endo.
The symptoms of this disease are many, often severe, and vary greatly from person to person. The only way to know if someone has a problem is surgery.
Even when diagnosed, finding effective medications that reduce symptoms without causing side effects or ulcers is a challenge for many patients.
Surgery and physical therapy are the treatment options offered today, but they do not work the same for everyone. Some researchers suspect that this is because endo includes several different types of conditions that may require different treatment options.
If true, future genetic research will be important in separating the different ways endometriosis can develop and what to do about it.
This study was published in Nature Genetics.
