Garitazelaia Aiara, Rueda-Martínez Aintzane, Arauzo Rebeca, de Miguel Jokin, Cilleros-Portet Ariadna, Marí Sergi, Bilbao Jose Ramon, Fernandez-Jimenez Nora, García-Santisteban Iraia
Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU) and Biocruces-Bizkaia Health Research Institute, 48940 Leioa, Basque Country, Spain.
Spanish Biomedical Research Center in Diabetes and associated Metabolic Disorders (CIBERDEM), 28029 Madrid, Spain.
Life (Basel). 2021 Jan 3;11(1):24. doi: 10.3390/life11010024.
Endometriosis, one of the most common gynecological disorders, is a complex disease characterized by the growth of endometrial-like tissue in extra-uterine locations and is a cause of pelvic pain and infertility. Evidence from observational studies indicate that endometriosis usually appears together with several other phenotypes. These include a list of autoimmune diseases, most of them more prevalent in women, anthropometric traits associated with leanness in the adulthood, as well as female reproductive traits, including altered hormone levels and those associated with a prolonged exposure to menstruation. However, the biological mechanisms underlying their co-morbidity remains unknown. To explore whether those phenotypes and endometriosis share a common genetic origin, we performed a systematic Two-Sample Mendelian Randomization (2SMR) analysis using public GWAS data. Our results suggest potential common genetic roots between endometriosis and female anthropometric and reproductive traits. Particularly, our data suggests that reduced weight and BMI might be mediating the genetic susceptibility to suffer endometriosis. Furthermore, data on female reproductive traits strongly suggest that genetic variants that predispose to a more frequent exposure to menstruation, through earlier age at menarche and shorter menstrual cycles, might also increase the risk to suffer from endometriosis.
子宫内膜异位症是最常见的妇科疾病之一，是一种复杂的疾病，其特征是子宫外位置出现类似子宫内膜的组织生长，是盆腔疼痛和不孕的原因。观察性研究的证据表明，子宫内膜异位症通常与其他几种表型同时出现。这些包括一系列自身免疫性疾病，其中大多数在女性中更为普遍，与成年期消瘦相关的人体测量特征，以及女性生殖特征，包括激素水平改变和与长期暴露于月经相关的特征。然而，它们共病的生物学机制仍然未知。为了探索这些表型与子宫内膜异位症是否有共同的遗传起源，我们使用公开的全基因组关联研究（GWAS）数据进行了系统的两样本孟德尔随机化（2SMR）分析。我们的结果表明子宫内膜异位症与女性人体测量和生殖特征之间可能存在共同的遗传根源。特别是，我们的数据表明体重和体重指数降低可能介导了患子宫内膜异位症的遗传因素。此外，关于女性生殖特征的数据强烈表明，通过初潮年龄较早和月经周期较短导致更频繁暴露于月经的遗传变异，也可能增加患子宫内膜异位症的风险。
