Endometriosis and Genetics: Is it Hereditary?

The Human Genome Project, which lasted 13 years and concluded in 2003, created a model DNA. This model is compared to an individual's DNA. Genetic differences (variants) are considered responsible for the hereditary component of diseases. If the genetic variants of endometriosis were identified, the disease could be treated in a personalized manner, and potentially predicted before it manifests, thus delaying its effects. However, this goal is still far off.

Endometriosis is so mysterious that researchers do not even know where to start. Which chromosomes and genes should be examined? Entire genomes of women with endometriosis (within the same family or population) are compared blindly, hoping that significant genetic variants will emerge.

This results in a massive amount of data, which modern technologies can produce, but which researchers paradoxically do not know how to interpret.

Endometriosis is a complex disease caused by a combination of multiple factors, both genetic and environmental. This means that hereditary genetic variants associated with endometriosis represent only a part of the risk of developing the disease. These variants confer genetic susceptibility to the disease, but environmental factors and lifestyle also play an important role, either through interaction with genetic factors or independently.

However, estimating familial aggregation of the disease is complicated by the fact that endometriosis is reliably diagnosed only through laparoscopy. The possibility of receiving an endometriosis diagnosis may be influenced by having a family member who has already been diagnosed with the disease; thus, obtaining a population-based risk estimate is difficult.

Studies on twins show a higher concordance in monozygotic twins compared to dizygotic twins. The largest study on twins, involving 3096 Australian twins, estimates the hereditary component of endometriosis at 51%.

In a study published in Nature Genetics, scientists compared the genomes of over 60,000 women with a confirmed diagnosis of the disease to those of about 700,000 healthy women. This large genome-wide association study aims to identify which genetic variants are most associated with a given disease. The analyses identified 42 genetic variants associated with endometriosis and other diseases like migraines, chronic back pain, asthma, and osteoarthritis.

PRACTICAL IMPLICATIONS

The findings of the study are extremely important as they precisely identify the genes involved in the disease's development. This means that by analyzing the genome of a person with endometriosis, it may be possible in the future to administer more targeted therapies based on the type of genetic "defect". The hope is to achieve personalized therapy, especially for those patients who do not benefit from hormonal treatments. The path is still long, but identifying the key players will allow the development of tailored treatments based on genetic characteristics.

NEW DRUGS

There are also new developments in treatments. Currently, there are no drugs other than hormonal ones available. This situation has been stagnant for 40 years but may soon change thanks to studies on dichloroacetate, a molecule that can interfere with the metabolism of endometrial cells. Successfully tested in animal models, a clinical trial on 100 women will soon begin to evaluate the effectiveness of this molecule in inhibiting the abnormal growth of endometrial tissue outside its usual location.

1. New Insights into Genetics of Endometriosis
   This comprehensive review explores genetic contributions to endometriosis and their potential impact on improving diagnostic techniques.
   Link to article
2. Genomics of Endometriosis: From Genome Wide Association Studies to Exome Sequencing
   This article discusses genetic influences on endometriosis, including findings from genome-wide association studies (GWAS) and exome sequencing.
   Link to article
3. Whole-exome sequencing reveals candidate high-risk susceptibility variants for endometriosis
   This study identifies genetic variants associated with endometriosis through whole-exome sequencing, highlighting the complexity of the disease's genetic basis.
   Link to article
4. Genetic Characterization of Endometriosis Patients
   This article reviews the literature on genetic characterization in endometriosis patients and presents findings from a prospective cohort study.
   Link to article
5. Defining the genetic profile of endometriosis
   This review discusses gene-gene and gene-environment interactions involved in endometriosis and summarizes various genetic studies conducted on the disease.
   Link to article
6. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions
   This meta-analysis identifies significant loci associated with endometriosis and explores their relationship with other pain conditions.
   Link to article