• Unraveling the Heritable Components of Endometriosis Using Whole Exome Sequencing in Personalized Medicine
  • Zahra Allahyar,1 Mona Khosravifar,2 Amir AmiriYekta,3 kiandokht Kiani,4,*
    1. Department of Genetics ,Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR ,Tehran ,Iran
    2. Department of Genetics ,Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR ,Tehran ,Iran
    3. Department of Genetics ,Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR ,Tehran ,Iran
    4. Department of Endocrinology and Female Infertility ,Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR ,Tehran ,Iran


  • Introduction: The document provides an overview of the use of whole-exome sequencing (WES) in the study of endometriosis, a common gynecological condition affecting around 10% of women. Endometriosis is a complex, estrogen-dependent condition characterized by the presence of endometrial-like tissue outside the uterus, which can lead to pain and infertility. Genetic factors play a significant role in endometriosis, with heritability estimates up to 50%. However, traditional genetic approaches like genome-wide association studies (GWAS) have limitations in identifying rare genetic variants. WES, which focuses on the genome's protein-coding regions, has emerged as a powerful tool to uncover rare pathogenic variants associated with endometriosis, especially in familial cases.
  • Methods: The following electronic databases were searched up to September 2024: Medline (PubMed platform) and Scopus. We use only English-language papers in our searches or study selection, with keywords such as Endometriosis and Whole Exome Sequencing.
  • Results: Several genes, including ARID1A, PIK3CA, KRAS, and PTEN, have been repeatedly identified in WES studies of endometriosis and related conditions like ovarian cancer, highlighting their potential importance in the pathogenesis of the disease. Integrating advanced genetic techniques like WES with accurate clinical diagnoses and comprehensive data analysis can provide valuable insights into the genetic basis of endometriosis and aid in the development of improved diagnostic and therapeutic strategies. The limitations of traditional genetic approaches like genome-wide association studies (GWAS) in studying endometriosis include their reduced ability to identify rare genetic variants, which are often associated with complex conditions like endometriosis. GWAS primarily focuses on common genetic variants and may overlook rare variants that could play a significant role in the pathogenesis of endometriosis. Additionally, GWAS may not fully capture the genetic heterogeneity and complexity of endometriosis, limiting its ability to provide a comprehensive understanding of the condition's genetic basis. Whole-exome sequencing (WES) and genome-wide association studies (GWAS) differ in their approaches to identifying genetic variants associated with endometriosis in the following ways: 1. Scope of analysis: - GWAS focuses on analyzing common genetic variants across the entire genome, typically single-nucleotide polymorphisms (SNPs). - WES targets the protein-coding regions of the genome, known as the exome, which account for approximately 1-2% of the total genome. 2. Variant detection: - GWAS is designed to detect common genetic variants that may have small to moderate effects on the risk of developing endometriosis. - WES is more effective in identifying rare and potentially pathogenic variants, including single-nucleotide variants (SNVs) and small insertions/deletions (indels), which may have larger effects on the disease. 3. Genetic architecture: - GWAS is well-suited for identifying common genetic variants that contribute to the polygenic nature of endometriosis. - WES can uncover rare variants that may be associated with familial or monogenic forms of endometriosis, providing insights into the genetic heterogeneity of the disease. 4. Clinical implications: - GWAS findings can help understand the overall genetic risk and susceptibility to endometriosis at the population level.
  • Conclusion: In conclusion, the integration of advanced genetic techniques like whole-exome sequencing (WES) with clinical data can help in understanding the pathogenesis of endometriosis by providing a comprehensive view of the genetic factors contributing to the condition. This approach allows for the identification of rare pathogenic variants associated with endometriosis, especially in familial cases, and can reveal insights into the underlying genetic mechanisms of the disease. Additionally, integrating WES with clinical data can aid in the development of improved diagnostic and therapeutic strategies tailored to the genetic profiles of individuals with endometriosis.
  • Keywords: Endometriosis , Hereditary , Whole Exome Sequencing, Personalized Medicine ,