An international team of researchers recently published the largest genetic study to date focused on endometriosis, and the data suggests that genetic links exist between endometriosis and conditions such as migraine and back pain.

The study, published in Nature Genetics, was conducted by the International Endometriosis Genomics Consortium, or IEGC, which is led by the University of Oxford in collaboration with 25 teams across the world.

Stacey Missmer, professor of obstetrics, gynecology and reproductive biology in the Michigan State University College of Human Medicine, discusses the study and its significance. Missmer is the U.S. leader of IEGC for the second phase of the study.

What is endometriosis?

Endometriosis is a condition primarily experienced by women who menstruate, impacting about one in 10 worldwide, or roughly 190 million girls and women.

Endometriosis is the presence of tissue that should only exist inside the uterus, or endometrium, but exists and grows outside of the uterus. While that tissue growth is associated with pelvic pain during menstruation, it also can cause pain at other times and without a predictable pattern. People with endometriosis have a higher risk of infertility, autoimmune conditions, heart conditions and ovarian cancer. 

How was this study conducted?

Researchers at the University of Oxford along with 25 teams across the world studied the DNA from 60,000 individuals who had been diagnosed with endometriosis and about 700,000 who had never been diagnosed with endometriosis. 

And among this very large collaborative data set, we identified 42 genes that were associated significantly with whether an individual had endometriosis. Then, we tried to determine whether those 42 genes could tell us something about the associations with specific symptoms that people with endometriosis present with.

What were some of your findings?

We found that the genes associated with endometriosis also had a high likelihood of being associated with other pain conditions like migraine, back pain and multisite chronic pain. We also found that these genes suggested a higher association with inflammatory and immune conditions such as asthma and osteoarthritis. These discoveries reinforce and bring more insight into our growing understanding of the effects of endometriosis beyond the reproductive system, and they have opened up many new areas of investigation.

It’s important to note that these 42 genes only explain about 5% of the risk of getting endometriosis, so if you wanted to use a test with these 42 genes to diagnose endometriosis, the test would fail miserably. We still have a lot more work to do to discover what explains the genetic heritability of endometriosis. But these study results are a leap forward in identifying genes associated with endometriosis and, more specifically, their function in the human body and the possible biology related to endometriosis risk.

This study also has reinforced and expanded the evidence that those with endometriosis have a higher risk of some other conditions later in life. Here we explored the genetic correlations with immune dysregulation and pain-associated conditions and were able to confirm that those with endometriosis have a higher risk of developing asthma, a higher prevalence of seasonal allergies and a higher risk of some autoimmune conditions. 

What do you think is the most important takeaway from your work on endometriosis?

I would say to those who are experiencing pelvic pain that they are far from alone and that they deserve to have their pain taken seriously and addressed to the best of our current clinical ability.

And I would urge health care providers to believe patients when they describe that they are experiencing pelvic pain and recognize that it is affecting their health and well-being. Taking pelvic pain symptoms seriously is something that not only clinicians can do immediately, but that friends and family support systems can also do to provide support. We can all help make sure that people don’t feel isolated in their pain and reassure them that what they’re experiencing is not only valid, but also very important to us.

What are the clinical applications of this study?
One applicable lesson for any clinician who treats patients with endometriosis is to know that your patients will have different symptoms and different responses to treatment. And it’s important to keep in mind that with regard to caring for the whole patient, these individuals may have health concerns that emerge that aren’t restricted to a gynecologist’s skill set and expertise and may require other clinical specialists. 

Listening to patients, asking them more detailed questions and formulating a broader plan for them are all strategies care providers can implement right now. 

It is going to take time to build the evidence that will define what it means to have different symptom presentation. The ultimate goal is to predict who will have different manifestations of endometriosis-associated symptoms and who is at greater risk for future additional morbidity.

Further, it will take time to discover treatments that might be specific to some subgroup of endometriosis but not to another and then provide clinicians with tools to predict how those different forms of endometriosis will respond to different treatments. Bottom line, clinicians need a larger and more precise toolkit to choose the best treatment plan for their individual patients.

What is next in this research?

This newly published study reflects our work identifying genes associated with overall endometriosis and determining whether those overall genes are still associated with subgroups. Now, we are going to start with the subgroups of endometriosis and see if there is something unique about them genetically.

Our research will seek to identify genes that maybe weren’t associated with endometriosis overall (the 42 identified genes), but are only associated with some of these subtypes. For example, a gene that is not associated with all endometriosis subtypes but is only associated with those who have ovarian endometriosis, or who experience bowel pain, or who also have migraines or who have asthma. 

The study was published in Nature Genetics.