Endometriosis rooted in genetics, say researchers

An international team of researchers have published the largest study to date on the genetic basis of endometriosis, suggesting 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 (IEGC), led by the University of Oxford in collaboration with 25 teams across the world.

It studied DNA from 60,600 women diagnosed with endometriosis and 701,900 without the condition, revealing evidence of a shared genetic basis for endometriosis and other types of pain seemingly unrelated to endometriosis, including migraine, back pain and multi-site pain.

Endometriosis, an inflammatory condition affecting 190 million women globally, can cause constant and intense pelvic pain, painful periods, painful bowel movements, excessive bleeding and, in some cases, infertility.

It is known that endometriosis can run in families, and therefore that genetic factors play a role in how it develops in some women but not in others.

The cause of the condition is unknown. Several theories have been suggested, including genetics and immune system problems.

Comparing the DNA code in women with and without the disease could, however, give scientists clues to the biological processes that are the basis for onset and progression.

The study conducted by IEGC identified 42 genes that were associated significantly with whether an individual had endometriosis.

By linking these variants to the profiles of molecules in endometrium and blood, researchers identified a range of genes that were differently expressed in these tissues and therefore had a likely role in disease development.

What they noted in particular is that many of the implicated genes play a role in pain perception and maintenance.

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, which could be related to so-called “sensitisation” of the central nervous system, which makes individuals suffering from chronic pain more prone to other types of pain.

Dr Nilufer Rahmioglu, senior research scientist at the Wellcome Centre for Human Genetics, University of Oxford, and first author of the study, said: “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.”

Professor Krina Zondervan, co-director of the Endometriosis CaRe Centre, and head of the Nuffield Department of Women’s & Reproductive Health, University of Oxford, senior author on the paper, added: “This study has provided a wealth of new knowledge on the genetics underlying endometriosis, which will 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.”

Discussing the study, Stacey Missmer, professor of obstetrics, gynaecology and reproductive biology at the Michigan State University College of Human Medicine and US leader of IEGC for the second phase of the study, said: “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.”