endometriosis genetics

Is Endometriosis Genetic? Understanding the Genetic Links in Endometriosis.

Endometriosis is a significant cause of discomfort and can greatly reduce the quality of life.  Although the disease’s origin remains somewhat elusive, research indicates a potential familial pattern. This article delves into the possible genetic basis of endometriosis, exploring its genetic and genomic aspects and their implications for improved diagnosis and treatment.

The Enigma of Endometriosis

Endometriosis is a condition where tissue similar to the endometrium – the internal lining of the uterus – grows outside the uterus. This can occur on the ovaries, fallopian tubes,the tissue lining the pelvis, and beyond. In some cases it grows superficially, in others it can invade deeply into other tissues or affect the ovaries. Despite extensive research, the exact cause of endometriosis and the reason for these variants remains an enigma. However, an interesting pattern has emerged over time – the disease appears to cluster in families, suggesting a potential genetic link.

Is Endometriosis Genetic?

Familial  predisposition suggests that endometriosis could be inherited in a polygenic or multifactorial manner. Polygenic or multifactorial inheritance refers to a condition that is affected by multiple genes (polygenic) and influenced by environmental factors (multifactorial).  Since everyone is different, this may also help explain why some people get one variant of the disease and others do not.  

Several factors make it difficult to understand the genetic link in endometriosis. The foremost is the diagnostic method. Endometriosis can only be definitively diagnosed through invasive procedures like laparoscopy or laparotomy. This can often lead to under-reporting of the disease with many people walking around undiagnosed for years. Another factor is the disease’s heterogeneous nature mentioned above, as it can manifest in different variants and locations within the body, suggesting potentially diverse disease processes.  Once these genetic links, which likely overlap, are unraveled and mapped then we will be able to diagnose endometriosis through blood tests rather than surgery.  Each genetic link eventually leads to molecular signals which can be used for diagnosis, treatment and follow-up monitoring.  

Familial Clustering and Evidence

Epidemiologic research has shown a familial clustering of endometriosis, meaning it appears more frequently within families. However, it does not seem to follow a simple Mendelian inheritance pattern. This observation supports multiple genetic factors contributing to the disease, consistent with polygenic/multifactorial inheritance and environmental impact.  

Genetic Mapping and Endometriosis

Gene mapping is a technique used to investigate potential gene mutations or polymorphisms associated with diseases like endometriosis. This method involves looking at the genome for excess sharing of informative polymorphic microsatellite markers in affected siblings. Studies using this method have highlighted areas in chromosomes 10 and 20 that may be linked to endometriosis. Despite the identification of these risk loci, the exact mechanism by which these genes influence the development of endometriosis is not yet fully understood.  So this association means someone may be at higher risk but does not guarantee that endometriosis will actually develop in any given individual. 

Genome-Wide Association Studies

Genome-Wide Association Studies (GWAS) represent a very promising method used to identify differences in the genetic makeup of individuals that could be responsible for variations in disease susceptibility. Basically, they compare the genomes of people with a certain disease (like endometriosis) to healthy individuals to look for genetic differences.

GWAS scans the genome of individuals for small variations, called single nucleotide polymorphisms (SNPs), that occur more frequently in people with a particular disease than in people without the disease. Each study can look at hundreds or thousands of SNPs at the same time. Then statistical methods can help identify which SNPs are associated with the disease.

First, genetic markers identified through GWAS could potentially be used to develop a genetic test for endometriosis. This could enable earlier and more accurate diagnosis of the disease, which is often difficult to diagnose due to its nonspecific symptoms and the need for invasive procedures to confirm diagnosis.

Second, as an example of treatment potential,  if a GWAS identifies a SNP in a gene involved in inflammation that is associated with endometriosis, researchers could develop a drug that targets this gene to reduce inflammation and treat endometriosis.  There are many other potential molecular pathways that influence endo development and progression that can and will be targeted.  

Genomics of Endometriosis

While genetics refers to the inheritance of a trait, genomics focuses on how genes are expressed, meaning how they are turned into structural proteins and signals and so forth. Genomics studies have identified significant alterations in gene expression in endometriosis, providing major insights into underlying biology. Genomic studies will likely lead to new noninvasive diagnostic strategies and possible new therapies. 

So, deeper understanding of endometriosis genomics can provide insights into the biological pathways and processes involved in the disease.  This can, in turn, inform diagnosis, treatment, and monitoring strategies.

Diagnosis:

When we better understand the genomics of endometriosis, we will be able to develop non-invasive non-surgical diagnostic tests. For example, if certain genetic variants are found to be associated with endometriosis, a simple blood test could be developed to look for these variants.

In addition to these genetic tests, understanding the molecular signaling pathways involved in endometriosis could potentially lead to the development of biomarker-based tests. Biomarkers are substances, such as proteins, that are indicative of certain biological conditions, like inflammation or fibrosis formation. If certain molecules are found to be elevated or decreased in women with endometriosis, these could be used as biomarkers for the disease.

Read more: The Different Tests Used to Diagnose Endometriosis 

Treatment:

Current treatments for endometriosis are basically limited to hormonal-based therapy, pain management, and surgery. However, these approaches do not work for everyone and can have significant short and long-term side effects. Short of a complete excision surgery, which is the cornerstone of today’s therapy, these are not curative therapies. Despite world-class excision surgery microscopic invisible post-surgical residual remains a concern and we need better options to eliminate anything that might be left in order to minimize or eliminate risk of recurrence.   

By understanding the genes and molecular pathways involved in endometriosis, we can identify new targets for biological drug development. For example, if a certain gene is found to be overactive in endometriosis, an agent could be developed to inhibit this gene. Similarly, some protein-based molecular pathways can be selectively inhibited. This is reality today in many diseases and there is no reason that endometriosis should not be amenable to similar options. 

Read more: Why You Need an OB-GYN Who Specializes in Endometriosis

Monitoring:

Lastly, understanding the genomics of endometriosis could also improve disease monitoring. For example, if certain genetic variants or molecular signals are associated with disease progression, these could potentially be used to monitor disease progression or response to treatment. This could lead to more personalized treatment strategies and improve patient outcomes.  To the point of microscopic residual after excision surgery, if none is likely present and no signals point to that, then no additional therapy would be required.  On the other hand, if there is molecular evidence to support possible micro-residual then treatment might be initiated right away, or at least at the time of first molecular evidence of recurrence or progression. 

The caveat here is that the translation of genomic and molecular research into clinical practice is a complex process that requires extensive further research and validation. It’s also worth noting that endometriosis is a complex disease likely influenced by a combination of genetic, environmental, and hormonal factors, and understanding these will be crucial for developing better diagnostic and treatment strategies. 

Read more: Debunking the Myths About Endometriosis & Exploring the Facts

Concluding Thoughts

The notion of endometriosis being genetic is supported by a growing body of research, highlighting the disease’s intricate and multifaceted nature. While our understanding of the genetics and genomics of endometriosis is still evolving, it holds the promise of improved diagnosis and treatment methods in the future. By continuing to explore the genetic foundations of this disease, we move closer to empowering those affected by endometriosis with knowledge and more effective treatment options.

In the end, unlocking the genetic and genomic secrets of endometriosis will pave the way for a future where this enigmatic condition is better understood, diagnosed, and treated.  While a lot of the above is in research or upcoming, some is available now.  Seek out an endometriosis expert who can discuss these with you and individualize a treatment plan.

Reference: 

Diana Maria Chiorean et al. New Insights into Genetics of Endometriosis—A Comprehensive Literature Review: Diagnostics (Basel). 2023 Jul; 13(13): 2265.

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