Genetic Link to Endometriosis – Unique Icelandic Study

28 February 2002

A woman has more than five times the normal risk of developing endometriosis if her sister has the
disease, according to research published today
(Thursday 28 February) in Europe’s leading
reproductive medicine journal, Human Reproduction*.

Moreover, even having a cousin with endometriosis
raises a woman’s risk by over 50%, according to the Icelandic team who carried out the research.

This is the first study to analyse the occurrence of
endometriosis across an entire population, and to
demonstrate an increased likelihood of developing
the disease between relatives outside the nuclear
family. It thus provides evidence of a significant
genetic component to endometriosis, as well as a
unique framework for identifying key genes involved in the development of the disease.

deCODE genetics, whose scientists led the research team, plans to use this information to develop a DNA-based test that can identify women at risk and make non-surgical diagnosis possible. This information will also be used to try to discover new treatments.

Endometriosis is a painful and distressing condition
in which endometrial tissue, which under normal
circumstances is found only in the lining of the
womb, develops outside the uterus and attaches itself to ligaments and organs in the abdominal cavity. This tissue responds to the menstrual cycle as though it were still inside the uterus. The repeated growth and disintegration of endometrial tissue in the abdomen can cause bleeding, pain, inflammation, adhesions and infertility. Between 1 and 5 percent of women are thought to suffer from endometriosis in their reproductive years.

The scientists from deCODE genetics and Iceland’s
National University Hospital, both based in Reykjavik, used deCODE’s unique genealogical database for the study. This computerised database includes the entire present-day Icelandic population of 290,000, as well as nearly 85% of all the Icelanders who have lived to adulthood since the country was settled in the ninth century.

“By using our population-wide genealogical resources and statistical models for measuring kinship, we have for the first time demonstrated the existence of a hereditary component to endometriosis that can be traced beyond first-generation relatives,” said Dr Kari Stefansson, Chief Executive Officer of deCODE and
co-author of the article. “This could not have been
achieved anywhere else in the world. The study is also important as the basis for a genome-wide scan to identify key genes that contribute to the disease. We are advancing in this effort, which we hope will contribute to the development of a DNA-based diagnostic test. Such a test would assist in diagnosing the disease and in identifying women at particular risk of endometriosis, without
the need for invasive procedures.”

Assisted by Professor Reynir Geirsson, chairman of the Department of Obstetrics and Gynecology at the National University Hospital, the researchers compiled a list of all 750 women in Iceland who had a surgical diagnosis of endometriosis between 1981 and 1993. This list was then run against deCODE’s geneaology database to analyse the women’s family connections. Applying several measures of familiality, deCODE’s scientists
demonstrated that the affected women were
significantly more interrelated than matched control
groups, highlighting the involvement of inherited
factors. All data on individuals in this research were anonymized and encrypted by the Icelandic government’s Data Protection Authority.

Although other research has reported an increased risk of endometriosis between first-degree relatives with the disease, this is the first in the world to demonstrate the link with cousins.

“It is extremely difficult in most countries to
discover whether second, third and fourth degree
relatives – and even more distant relatives – have
the disease. This is due in part to the fact that
endometriosis requires invasive surgery for accurate diagnosis, and is thus severely under diagnosed. Furthermore, people often don’t know who their non-immediate relatives are or, if they do, may not feel close enough to speak about medical histories,” said Dr Stefansson. “This has made it exceedingly difficult for researchers elsewhere to look at the disease beyond the nuclear family.”

Commented Professor Geirsson: “We found that among sisters there was a 5.2-fold increase in the risk of being diagnosed with endometriosis. The risk among first cousins was lower, but still significantly higher than in the control groups. Sisters share half of their genomes, but cousins share 12.5% and the difference seen for the latter group may therefore more accurately reflect the genetic liability.”

The research team emphasised that establishing the link between cousins was a crucial achievement. By looking at the population as a whole rather than just immediate family groups, and by counting only one member of each cluster of first degree relatives when calculating the relatedness of those with the disease, they had minimised bias. They had also gained a much
more accurate picture of endometriosis risk in a
society, rather than simply in a nuclear family. From
the inheritance pattern seen in the study it was also
evident that the genetic factors involved in
endometriosis can be inherited through paternal as
well as maternal lines.

One message to emerge from the study is that women who want children but have endometriosis in the family might consider pregnancy earlier rather than later in their reproductive life, as the condition does tend to progress with time. Also, if a woman had many of the symptoms of endometriosis and a relative with the condition, she and her doctor may want to consider her having a laparoscopy to confirm or rule-out the condition.

* Genetic factors contribute to the risk of developing endometriosis. Human Reproduction.
Vol.17. No.3. pp 555-559.

Source: Human Reproduction (Journal of the European Society of Human Reproduction and Embryology)

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