Evidence of shared genetic factors in the etiology of gastrointestinal disorders and endometriosis and clinical implications for disease management

Yang, Fei; Wu, Yeda; Hockey, Richard; Doust, Jenny; Mishra, Gita D.; Montgomery, Grant W.; Mortlock, Sally

doi:10.1016/j.xcrm.2023.101250

Cited by 7 publications

(9 citation statements)

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“…further add to our understanding of the genetic causes of endometriosis and its associated symptoms with new information that provides evidence that endometriosis shares genetic risk factors with several common GI disorders. 1 The results extend those of a genetic analysis of shared risk factors between depression and endometriosis, where “abnormality of the gastric mucosa” showed a statistical enrichment. 5 …”

Section: Main Textsupporting

confidence: 67%

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Genetic analysis confirms a link between gastrointestinal disorders and endometriosis

Saunders,

Horne

2023

Cell Reports Medicine

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Section: Main Textsupporting

confidence: 67%

“…Yang et al. 1 identify genetic risk factors that can contribute to a shared disease etiology, providing new opportunities for improvements in disease management.…”

mentioning

confidence: 99%

Genetic analysis confirms a link between gastrointestinal disorders and endometriosis

Saunders,

Horne

2023

Cell Reports Medicine

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“…The genetics and the immune system trigger the intrinsic changes in the endometrium 4 . EM presents a genetic correlation (rg) with various diseases associated with inflammation and chronic pain 5,6 . The estimated heritability rate is up to 50% 6 .…”

Section: Introductionmentioning

confidence: 99%

“…diseases associated with inflammation and chronic pain. 5,6 The estimated heritability rate is up to 50%. 6 Genetic prediction is vital for the assessment of EM in its development and malignancy.…”

mentioning

confidence: 99%

Heme metabolism and HO‐1 in the pathogenesis and potential intervention of endometriosis

Hou,

Lu,

Zhang

et al. 2024

American J Rep Immunol

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Endometriosis (EM) is one of the diseases related to retrograded menstruation and hemoglobin. Heme, released from hemoglobin, is degraded by heme oxygenase‐1 (HO‐1). In EM lesions, heme metabolites regulate processes such as inflammation, redox balance, autophagy, dysmenorrhea, malignancy, and invasion, where macrophages (Mø) play a fundamental role in their interactions. Regulation occurs at molecular, cellular, and pathological levels. Numerous studies suggest that heme is an indispensable component in EM and may contribute to its pathogenesis. The regulatory role of heme in EM encompasses cytokines, signaling pathways, and kinases that mediate cellular responses to external stimuli. HO‐1, a catalytic enzyme in the catabolic phase of heme, mitigates heme's cytotoxicity in EM due to its antioxidant, anti‐inflammatory, and anti‐proliferative properties. Certain compounds may intervene in EM by targeting heme metabolism, guiding the development of appropriate treatments for all stages of endometriosis.

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“…Whilst the flagship symptoms of endometriosis are pelvic pain and infertility, it is now appreciated endometriosis patients will often exhibit disturbances to multiple bodily systems beyond the reproductive system. Recently, a wealth of epidemiological data has identified many conditions that are comorbid with endometriosis, multiple of which have evidence of a shared genetic architecture [ 3 – 6 ]. An understanding of the overlapping traits with endometriosis is critical for comprehensive health management of the patient, for developing predictive tools, and for elucidating the underlying biology of endometriosis.…”

Section: Introductionmentioning

confidence: 99%

Polygenic risk score phenome-wide association study reveals an association between endometriosis and testosterone

McGrath,

Montgomery,

Mortlock

2023

BMC Med

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Background Endometriosis affects 1 in 9 women, yet it is poorly understood with long diagnostic delays, invasive diagnoses, and poor treatment outcomes. Characterised by the presence of endometrial-like tissue outside of the uterus, its main symptoms are pain and infertility. Endometriosis often co-occurs with other conditions, which may provide insights into the origins of endometriosis. Methods Here a polygenic risk score phenome-wide association study of endometriosis was conducted in the UK Biobank to investigate the pleiotropic effects of a genetic liability to endometriosis. The relationship between the polygenic risk score for endometriosis and health conditions, blood and urine biomarkers and reproductive factors were investigated separately in females, males and females without an endometriosis diagnosis. The relationship between endometriosis and the blood and urine biomarkers was further investigated using genetic correlation and Mendelian randomisation approaches to identify causal relationships. Results Multiple health conditions, blood and urine biomarkers and reproductive factors were associated with genetic liability to endometriosis in each group, indicating many endometriosis comorbidities are not dependent on the physical manifestation of endometriosis. Differences in the associated traits between males and females highlighted the importance of sex-specific pathways in the overlap of endometriosis with many other traits. Notably, an association of genetic liability to endometriosis with lower testosterone levels was identified. Follow-up analysis utilising Mendelian randomisation approaches suggested lower testosterone may be causal for both endometriosis and clear cell ovarian cancer. Conclusions This study highlights the diversity of the pleiotropic effects of genetic risk to endometriosis irrespective of a diagnosis of endometriosis. A key finding was the identification of a causal effect of the genetic liability to lower testosterone on endometriosis using Mendelian randomisation.

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Evidence of shared genetic factors in the etiology of gastrointestinal disorders and endometriosis and clinical implications for disease management

Cited by 7 publications

References 105 publications

Genetic analysis confirms a link between gastrointestinal disorders and endometriosis

Genetic analysis confirms a link between gastrointestinal disorders and endometriosis

Heme metabolism and HO‐1 in the pathogenesis and potential intervention of endometriosis

Polygenic risk score phenome-wide association study reveals an association between endometriosis and testosterone

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