Largest Genetic Study of Endometriosis Identifies New Risk Factors
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The largest genetic study of endometriosis conducted to date has revealed new insights on key variants that increase disease risk. The research, led by Oxford University’s Professor Krina Zondervan and Dr. Nilufer Rahmioglu in collaboration with 24 research teams from across the world, is published in Nature Genetics.
A new GWAS study of endometriosis
Endometriosis is an inflammatory condition where cells of the uterine lining – or cells similar to endometrial tissue – grow outside of the uterus. It affects approximately one in nine women globally, and patients with the disorder can experience chronic pelvic pain, bowel and bladder dysfunction, headaches, fatigue and an overall decreased quality of life.
“Very little is known about the causes of endometriosis, but studying genetics can give us clues to the biological processes that are the basis for onset and progression,” says Dr. Sally Mortlock, a research fellow at the University of Queensland and a co-author of the new study.
The researchers conducted a genome-wide association study (GWAS) of 60,674 women with endometriosis and 701,926 women without endometriosis as a control group, using data from the UK Biobank and 23andMe.
What is a GWAS study?
A GWAS is a research method commonly used in genetics research, which involves studying a cohort of individuals that possess a specific phenotype, for example, having a disease such as endometriosis, and comparing their genetics to individuals that do not have that disease. By scanning the genome for single nucleotide polymorphisms (SNPs) – a common type of genetic variant – researchers can understand whether certain variants occur in higher frequencies in individuals with that disease. If this is the case, the genetic variants are classed as being associated with the disease – i.e., they typically occur more often in people suffering from the disease, than people that don’t.
While association implies a link between the variant and the disease, it does not prove causation. Nonetheless, GWAS studies can serve as powerful tools to identify regions of the human genome where disease-causing problems may exist.
Forty-two associations discovered
Prior to the new study, a total of 17 genetic regions were known to be associated with endometriosis. Zondervan and colleagues identified 42 genome-wide significant loci associated with the condition which, according to Mortlock, means, “we can find out what genes in these regions do and find new drug targets, leading to new treatments.” Examples of the associated genes include SRP14/BMF, GDAP1, MLLT10, BSN and NGF, which are implicated in pain perception and maintenance.
The researchers also discovered that certain genetic risk factors associated with endometriosis are also associated with other conditions. “We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis,” they write in the paper.
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These links with pain conditions that appear unrelated to endometriosis might suggest a “sensitization” occurring within the central nervous system, Mortlock says: “This makes people suffering from chronic pain more prone to other types of pain.”
To further advance the work, the research team say that targeted investigations of genetically regulated mechanisms that appear in endometriosis and other conditions are required, to “aid the development of new treatments and facilitate early symptomatic intervention.” “Perhaps in some cases, we need to be designing pain treatments rather than hormonal treatments,” Matlock concludes.
Reference: Rahmioglu N, Mortlock S, Ghiasi M, et al. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Gen. 2023;55(3):423-436. doi:10.1038/s41588-023-01323-z
This article is a rework of a press release issued by the University of Queensland. Material has been edited for length and content.