BACKGROUND Endometriosis remains a poorly understood disease, despite its high prevalence and debilitating symptoms. The overlap in symptoms and the increased risk of multiple other traits in women with endometriosis is becoming increasingly apparent through epidemiological data. Genetic studies offer a method of investigating these comorbid relationships through the assessment of causal relationships with Mendelian randomization (MR), as well as identification of shared genetic variants and genes involved across traits. This has the capacity to identify risk factors for endometriosis as well as provide insight into the aetiology of disease. OBJECTIVE AND RATIONALE We aim to review the current literature assessing the relationship between endometriosis and other traits using genomic data, primarily through the methods of MR and genetic correlation. We critically examine the limitations of these studies in accordance with the assumptions of the utilized methods. SEARCH METHODS The PubMed database was used to search for peer-reviewed original research articles using the terms ‘Mendelian randomization endometriosis’ and ‘“genetic correlation” endometriosis’. Additionally, a Google Scholar search using the terms ‘“endometriosis” “mendelian randomization” “genetic correlation”’ was performed. All relevant publications (n = 21) published up until 7 October 2022 were included in this review. Upon compilation of all traits with published MR and/or genetic correlation with endometriosis, additional epidemiological and genetic information on their comorbidity with endometriosis was sourced by searching for the trait in conjunction with ‘endometriosis’ on Google Scholar. OUTCOMES The association between endometriosis and multiple pain, gynaecological, cancer, inflammatory, gastrointestinal, psychological, and anthropometric traits has been assessed using MR analysis and genetic correlation analysis. Genetic correlation analyses provide evidence that genetic factors contributing to endometriosis are shared with multiple traits: migraine, uterine fibroids, subtypes of ovarian cancer, melanoma, asthma, gastro-oesophageal reflux disease, gastritis/duodenitis, and depression, suggesting the involvement of multiple biological mechanisms in endometriosis. The assessment of causality with MR has revealed several potential causes (e.g. depression) and outcomes (e.g. ovarian cancer and uterine fibroids) of a genetic predisposition to endometriosis; however, interpretation of these results requires consideration of potential violations of the MR assumptions. WIDER IMPLICATIONS Genomic studies have demonstrated that there is a molecular basis for the co-occurrence of endometriosis with other traits. Dissection of this overlap has identified shared genes and pathways, which provide insight into the biology of endometriosis. Thoughtful MR studies are necessary to ascertain causality of the comorbidities of endometriosis. Given the significant diagnostic delay of endometriosis of 7–11 years, determining risk factors is necessary to aid diagnosis and reduce the disease burden. Identification of traits for which endometriosis is a risk factor is important for holistic treatment and counselling of the patient. The use of genomic data to disentangle the overlap of endometriosis with other traits has provided insights into the aetiology of endometriosis.

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孟德尔随机化和遗传相关分析对子宫内膜异位症及其合并症之间关系的见解

背景技术尽管子宫内膜异位症患病率高并且症状令人衰弱，但它仍然是一种人们知之甚少的疾病。通过流行病学数据，子宫内膜异位症女性的症状重叠和多种其他特征的风险增加变得越来越明显。遗传学研究提供了一种通过孟德尔随机化 (MR) 评估因果关系以及识别跨性状涉及的共享遗传变异和基因来研究这些共病关系的方法。这能够识别子宫内膜异位症的危险因素，并深入了解疾病的病因。目的和基本原理我们的目的是回顾当前利用基因组数据评估子宫内膜异位症与其他性状之间关系的文献，主要通过MR和遗传相关的方法。我们根据所用方法的假设严格审查这些研究的局限性。搜索方法 PubMed 数据库用于使用术语“孟德尔随机化子宫内膜异位症”和““遗传相关”子宫内膜异位症”来搜索同行评审的原始研究文章。此外，还使用术语“子宫内膜异位症”“孟德尔随机化”“遗传相关性”进行了谷歌学术搜索。截至 2022 年 10 月 7 日发表的所有相关出版物 (n = 21) 均包含在本次审查中。在对已发表的 MR 和/或与子宫内膜异位症遗传相关的所有性状进行汇编后，通过在 Google 学术搜索上结合“子宫内膜异位症”搜索该性状，获得了有关其与子宫内膜异位症合并症的额外流行病学和遗传信息。结果 使用 MR 分析和遗传相关分析评估了子宫内膜异位症与多种疼痛、妇科、癌症、炎症、胃肠道、心理和人体测量特征之间的关联。遗传相关分析提供的证据表明，导致子宫内膜异位症的遗传因素与多种特征共有：偏头痛、子宫肌瘤、卵巢癌亚型、黑色素瘤、哮喘、胃食管反流病、胃炎/十二指肠炎和抑郁症，这表明多种生物学因素参与其中。子宫内膜异位症的机制。MR 因果关系的评估揭示了子宫内膜异位症遗传易感性的几个潜在原因（例如抑郁症）和结果（例如卵巢癌和子宫肌瘤）；然而，解释这些结果需要考虑可能违反 MR 假设的情况。更广泛的影响 基因组研究表明，子宫内膜异位症与其他性状同时发生有分子基础。对这种重叠的剖析确定了共享的基因和途径，这为了解子宫内膜异位症的生物学提供了见解。为了确定子宫内膜异位症合并症的因果关系，需要进行深思熟虑的 MR 研究。鉴于子宫内膜异位症的诊断延迟了 7-11 年，因此有必要确定危险因素以帮助诊断并减轻疾病负担。识别子宫内膜异位症的危险因素对于患者的整体治疗和咨询非常重要。使用基因组数据来理清子宫内膜异位症与其他特征的重叠，为子宫内膜异位症的病因学提供了见解。