Largest ever genetic study of endometriosis completed

Researchers at the University of Oxford, in collaboration with 25 teams across the world, have published the largest study to date of the genetic basis of endometriosis, finding new data about the variants that increase risk of the disease. Published in the journal Nature Genetics, the study found genetic risk factors for endometriosis are also associated with other, seemingly unrelated, chronic pain types such as migraine, back pain and multi-site pain.

Endometriosis is a severe inflammatory condition occurring in 5–10% of women of reproductive age that is characterised by the presence of tissue that resembles the uterus lining (endometrium) outside the uterus. The location of these endometriotic deposits is primarily on organs within the pelvis, although more rarely it can also be found outside the pelvis. Often taking 8–10 years to diagnose from first symptoms, the condition can cause constant and intense pelvic pain, fatigue, depression, anxiety and infertility, and treatment is limited to repeated surgeries as well as hormonal treatments that do not allow women to get pregnant.

It is known that endometriosis can run in families and therefore that genetic factors (heritability) play a role in how it develops in some women but not in others. Very little is known about the causes of endometriosis, and studying genetics — by comparing the DNA code in women with and without the disease — can give us clues to the biological processes that are the basis for onset and progression.

With this in mind, the researchers analysed DNA from 60,600 women with endometriosis and 701,900 without — and found 42 areas across the genome that harbour variants that increase risk of endometriosis. Before this study, scientists were only aware of 17 of these regions.

By linking these gene variants to the profiles of molecules in endometrium and blood, the researchers identified a range of genes that were differently expressed in these tissues and therefore had a likely role in disease development. This list of genes is important for further work to develop of new treatments, better targeted to subtypes of disease. For instance, they found that some genetic variants were more associated with ovarian ‘cystic’ endometriosis than superficial disease spread throughout the pelvis.

What they noted in particular is that many of the implicated genes play a role in pain perception and maintenance. Indeed, they found that there was a shared genetic basis for endometriosis and a range of other chronic pain types such migraine, back pain and multi-site pain. This could be related to ‘sensitisation’ of the central nervous system, which makes individuals suffering from chronic pain more prone to other types of pain. These findings open up the possibility of designing new pain-focused non-hormonal treatments, or repurposing existing pain treatments, for endometriosis.

“Using different datasets of women with and without endometriosis, some of which had unprecedented detailed data on surgical findings and pain experience collected using standardised criteria, allowed us to generate a treasure trove of new information about genetically driven endometriosis subtypes and pain experience,” said first author Dr Nilufer Rahmioglu, Senior Research Scientist at Oxford’s Wellcome Centre for Human Genetics. These results should help the research community in their efforts to come up with new treatments and possibly new ways of diagnosing the disease, benefiting millions of women worldwide.

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