Genetics and stem cells

Endometriosis genetics explored

BBC News reported today that “gene research gives hope for women with endometriosis”. It said that research in more than 5,000 women had found clues for why endometriosis occurs in some women and not others. Sites on chromosomes 1 and 7 were identified as being crucial to a woman’s risk.

The news story is based on a large genetic study. The researchers identified a new genetic variant on chromosome 7 that is linked with the likelihood of a woman having endometriosis. This is a complex condition and its exact causes are unknown, but a number of factors are thought to be involved, including many genes and possibly some environmental factors.

Possessing the variant identified in this study does not mean that a woman is guaranteed to suffer from endometriosis and, in fact, the new variant was estimated to account for only a small amount of the variability in the condition's symptoms in a population.

Overall, this well-conducted study furthers our understanding of the contribution of genes to the risk of endometriosis. It remains to be seen whether the findings will contribute to new ways to diagnose or treat the disease.

Where did the story come from?

The study was carried out by researchers from the Queensland Institute of Medical Research in Australia, the University of Oxford, England and other academic and medical institutions across America, Australia and the UK. The study was funded by the Wellcome Trust, the National Health and Medical Research Council of Australia, the Cooperative Research Centre for Discovery of Genes for Common Human Diseases (CRC), Cerylid Biosciences (Melbourne) and donations from individuals. It was published in the peer-reviewed medical journal Nature Genetics.

The research was covered well by the BBC who broadly described the methods of the study and highlighted the context of the research, with quotes from lead researchers and experts in this condition.

What kind of research was this?

This was a genome-wide association (GWA) study, a common study type in the area of genetics. It is used to look for particular genetic sequences (variants) that differ between people with a condition and those without it. In essence, a GWA is a type of case control study, comparing two groups of people and linking their differences with their condition.

In this study, the researchers aimed to investigate in detail how genetics contribute to endometriosis, a relatively common disorder that affects women of reproductive age. About 2 million women in the UK are thought to have endometriosis; however, not all women show symptoms so the exact number of women who have it is not known. Estimates vary from about 1 in 10 to as many as 5 in 10 of all women will develop some degree of endometriosis during their lives.

It occurs when cells typically found inside the womb grow outside the uterine cavity. The exact causes are unclear but genetics are known to have a role. Symptoms can be severe and include pelvic pain, severely painful periods and the condition can affect fertility.

What did the research involve?

The researchers recruited 3,194 women who had surgically confirmed endometriosis from two different countries (Australia and UK). The women were separated into two groups depending on the severity of their disease. Group A women had less severe endometriosis and group B had more severe disease. The researchers in this study were particularly interested in how much genetics contributes to different severities of disease. They compared the DNA sequences of the two groups of women with endometriosis with 7,060 women who did not have the disease.

As is common in these studies, a second set of experiments was done where researchers investigated whether the genetic variants they identified in the first sample were still associated with the disease in a second, independent group. They repeated their experiment in a further 2,392 women with endometriosis and 2,271 controls from the US. Although the condition was not confirmed surgically in this sample, the researchers estimated that about 40% of the sample would have severe disease (as in the previous sample).

The researchers go on to discuss how their results differ and are similar to other studies in this area and present possible genetic explanations for why these variants may affect the risk of endometriosis. They also calculated how much of the ‘heritability’ of endometriosis can be explained by the variants they have identified. The heritability of a characteristic (in this case endometrosis) is a measure of how much genetic factors contribute to the differences between people in the population in this characteristic. Previous studies have estimated endometriosis to have a heritability of 51%.

What were the basic results?

Genetic differences were identified between women with both severities of endometriosis and the control group. These differences were greater in women with moderate to severe disease (group B). The contribution of all of the genetic variants that were assessed, to the risk of moderate to severe disease, was about 34% and contributed about 15% to the risk of less severe endometriosis (group A).

One particular variant on chromosome 7, called rs12700667, was strongly associated with endometriosis and the association was slightly greater in group B. Women with this variant were about 1.2 times more likely to have endometriosis and nearly 1.4 times more likely to have severe disease than those without the variant. Another nearby variant on chromosome 7 was also more common in women with severe endometriosis (rs7798431) than those without the condition, as was one on chromosome 2 (rs1250248).

In their second sample of cases and controls from the US, significant links were again seen with both variants on chromosome 7 (rs12700667 and rs7798431), but not with the variant on chromosome 2 (rs1250248).

It is estimated that about 51% of the variation in endometriosis symptoms between women in the populations is due to genetics. The researchers estimated that rs12700667 may explain about 0.69% of this 51%, i.e. a very small amount.

How did the researchers interpret the results?

The researchers conclude that they have identified a new variant on chromosome 7 that is associated with the development of endometriosis. They say that genetics may be more important for moderate to severe disease and that further studies in a large number of women with this severity will have greater power to identify other important variants.


This research was accurately reported and well conducted, using methods that are common in this field. The researchers have confirmed the findings of their initial experiments in a separate population - a common way to check results in studies of this kind. This study replicates the findings of some other work, but has also identified a new variant associated with endometriosis. There are a number of points that help with the interpretation of these results:

  • Having the variant on chromosome 7 does not mean that a woman will definitely develop endometriosis. This condition is complex and is only partially explained by genetics, and the new variant explains only a very small proportion of the genetic contribution to this disease. It is likely that a host of genetic and environmental factors work together to increase the risk in some women.
  • The genetic variant identified in this study does not lie within a gene and may itself not increase the risk of endometriosis. It may instead be situated near other genetic variations that have this effect. Further research is needed to investigate which nearby genes could be affecting a woman’s risk.
  • This complexity means that on its own, this new variant could actually contribute little to improvements in the diagnosis of endometriosis. It is possible that in the future, these findings could be combined with other identified variants, to develop tests to profile a woman’s risk of this condition. However, even tests such as this will not predict whether or not a woman will develop this disease, but simply point to women at potentially higher risk. Identifying women at greater risk of having the condition might not be helpful unless methods to prevent the condition developing are discovered.
  • Any new research into conditions that have unclear causes, and for which there are few treatment options, are welcome. The lead researchers are optimistic that their study will help towards developing less invasive diagnostic methods and more effective treatments for endometriosis. This remains to be seen.

Overall, this is a good study that increases our understanding of why some women may develop endometriosis over others.

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