Updates in the Field of Endometriosis: Genetics

Updates in the Field of Endometriosis: Genetics

Research has shown that individuals with a family history of endometriosis are more likely to get a severe form of the illness.

Key Points


  • This chapter by Krishnamoorthy and Decherney discuss the role of genetics in the disease progression of endometriosis.


  • Elucidating the genetic mechanism that underlies endometriosis disease progression will result in increased knowledge about the disease that can help in the conception of more effective therapies.

What’s done here?

  • The authors gathered information about the link between genetics and endometriosis. They interspersed this knowledge with relevant research.

Key Points:

  • Familial Aggregates: Several studies point to a familial tendency towards endometriosis. 
    • Women with a first-degree relative who has endometriosis have a 7-10 fold increase in their chances of getting endometriosis. Additionally, individuals with a first degree relative with the disease were more like to get a more severe form of the illness.
    • It is hypothesized that endometriosis is governed by single entity polygenic inheritance (an individual is more susceptible to get a severe form of endometriosis if more of their relatives have the disease).
  • Candidate Genes:  Research thus far showed a weak link to endometriosis at best, discrepancies stemming from varied ethnicities, small sample sizes, and the inability to reproduce the results.
    • The identified genes are steroid/hormone receptors, cytokines/inflammation factors, adhesion molecules as well as matrix enzymes, and cell cycle regulatory genes.
    • Sex steroid biosynthesis pathway associated with progesterone and estrogen receptors have been found to influence the progression of the disease, which includes CYP17, ER, PR, HSD17B1, and CYP19
    • N314D, a polymorphism of the GALT enzyme has been linked to ovarian cancer, Mullerian defects, and early menopause; have yet to be proven in endometriosis.
    • Deletions of the genes involved in the detoxification of estrogen and reactive oxygen species (GSTM1 and GSTT1) are thought to promote endometriosis.
  • Linkage Studies help researchers to identify genome areas that are likely to carry genetic abnormalities that will increase an individual’s risk for the disease.
    • Peaks of linkage were found on chromosomes 10q, 20p and 7p.
    • Similar to cancer, endometriosis causes a loss of heterozygosity, which leads to the loss of a tumor suppressor gene and the chromosome region around it. In endometriosis, this tends to occur at 5q, 6q, 9p, 11q and 22q. Other studies revealed that this loss occurred at the TP53 and PTEN tumor suppressor gene loci.
    • Bischoff and Simpson came up with a multi-hit strategy that states that the genes affected by an inheritance of familial mutation or somatic mutation from a sporadic disease that deals with cell attachment and persistence are the ones affected by the first hit. During menstruation, these individuals have mutated cells that will attach to their peritoneum and enable additional mutations that will result in endometriosis. In other words, genetics makes it so that an individual who suffers an altered first hit is more likely to develop endometriosis after a second hit.
    • Since linkage studies give a large area of genomic data from which it is hard to locate a single abnormality, researchers have turned to comparing single nucleotide polymorphisms (SNPs).
  • Genome Wide Association Studies (GWAS) Approach
    • GWAS looks at the entire genome for abnormalities by genotyping SNPs.
    • Studies using this method in two different countries have found genetic associations between endometriosis and the CDKN2BAS gene.
    • Another study found that down-regulation of HOXA10 can lead to endometriosis. It is found near SNP rs12700667.
    • A susceptibility locus was found close to the WNT4 gene.
    • There are some validated loci but they are inadequate, due to the number and inability to be affirmed. Thus they cannot help describe the heritability of the disease.
    • The authors maintain that the next step to identifying variations is DNA sequencing and continued GWAS use.

 This summary is a part of the future of endometriosis research, whic summarises the progress made in this field. The developments have been delineated in a 2017 issue of Clinical Obstetrics and Gynecology. For updates specific to a given topic namely surgery, epigenetics, imaging, fertility and fertility preservation, one can consult the issue above of Clinical Obstetrics and Gynecology or please look at the summaries for each topic, found in Endonews.

Lay Summary

This chapter written by Krishnamoorthy and Decherney re-evaluate the literature concerning the genetics of endometriosis. The genetic mechanisms and signaling pathways that led to endometriosis are updated and the tools that help researchers find these abnormal genes and pathways are summarized. 

The authors first prove that endometriosis has a genetic component to it since a woman with an immediate family member with the disease has a higher chance of getting the disease. Heritability has also been shown to increase the severity of the illness. The next part of this chapter focuses on the candidate genes, which are split into 4 groups. This section does identify some of the genes that have been found to influence endometriosis disease progression. The third section looks at linkage studies, which identify areas in the genome where certain abnormalities are usually found. Krishnamoorthy and Decherney also explain Bischoff and Simpson’s multi-hit strategy within this section, which states that an individual with an inherited abnormal gene is more likely to get endometriosis with a second hit that follows an altered first hit. Hit is defined as the attachment of mutated endometrial cells to the peritoneum. The final part of this chapter looks at the Genome Wide Association Studies (GWAS) approach. GWAS utilizes SNPs to identify abnormalities in the genome.

While a lot has been discovered about the link between endometriosis and genetics, the authors provide suggestions as to the next steps that should be taken to understand more about this relationship.

It is important to note that the full chapter on genetics and endometriosis can be found in a 2017 issue of Clinical Obstetrics and Gynecology. For updates specific to another given topic namely surgery, epigenetics, imaging, fertility and fertility preservation, one can consult the aforementioned issue of Clinical Obstetrics and Gynecology or look at the summaries found on today`s Endonews as an all-encompassing summary.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/28742585

Genetics GWAS Linkage studies SNPs


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