McGrath Isabelle M, Rukins Valentina, Laisk Triin, Mortlock Sally, Montgomery Grant W
The Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4072 QLD, Australia; Department of Psychiatry, University of Oxford, Oxford, UK.
Estonian Genome Center, Institute of Genomics, University of Tartu, 51010 Tartu linn, Estonia.
HGG Adv. 2025 May 13;6(3):100456. doi: 10.1016/j.xhgg.2025.100456.
Endometriosis is a complex disease, and many genetic and environmental risk factors contribute to disease risk. The genetic risk of endometriosis has been well characterized in genome-wide association studies. While few physiological risk factors are known, endometriosis is associated with many comorbid disorders. This study examines the interplay between genetic risk factors, comorbid disorders, and endometriosis. Genetic and health record data from the UK Biobank (5,432 cases; 92,344 controls) and Estonian Biobank (3,824 cases; 15,296 controls) was used to estimate the correlation between comorbidity burden, endometriosis and genetic risk, and to estimate the interactive effects between endometriosis polygenic risk score (PRS) and diagnosis of prevalent comorbidities (uterine fibroids, heavy menstrual bleeding, dysmenorrhea, irritable bowel syndrome, diverticular disease, and asthma) on endometriosis prevalence. The comorbidity burden was significantly higher in endometriosis cases and was positively correlated with endometriosis PRS in women without endometriosis but negatively correlated in women with endometriosis. The absolute increase in endometriosis prevalence conveyed by the presence of several comorbidities (uterine fibroids, heavy menstrual bleeding, dysmenorrhea) was greater in individuals with a high endometriosis PRS compared to a low endometriosis PRS. These findings, consistent across two biobanks, highlight significant interactions between polygenic risk for endometriosis and the diagnosed comorbidities in endometriosis susceptibility that have implications for understanding the underlying mechanisms contributing to disease risk.
子宫内膜异位症是一种复杂的疾病，许多遗传和环境风险因素都会增加患病风险。在全基因组关联研究中，子宫内膜异位症的遗传风险已得到充分表征。虽然已知的生理风险因素很少，但子宫内膜异位症与许多共病相关。本研究探讨了遗传风险因素、共病与子宫内膜异位症之间的相互作用。利用来自英国生物银行（5432例病例；92344例对照）和爱沙尼亚生物银行（3824例病例；15296例对照）的遗传和健康记录数据，来估计共病负担、子宫内膜异位症与遗传风险之间的相关性，并估计子宫内膜异位症多基因风险评分（PRS）与常见共病（子宫肌瘤、月经过多、痛经、肠易激综合征、憩室病和哮喘）诊断对子宫内膜异位症患病率的交互作用。子宫内膜异位症病例的共病负担显著更高，在没有子宫内膜异位症的女性中，共病负担与子宫内膜异位症PRS呈正相关，但在患有子宫内膜异位症的女性中呈负相关。与低子宫内膜异位症PRS的个体相比，高子宫内膜异位症PRS的个体中，几种共病（子宫肌瘤、月经过多、痛经）的存在使子宫内膜异位症患病率的绝对增加更大。这些在两个生物银行中一致的发现，突出了子宫内膜异位症多基因风险与子宫内膜异位症易感性中已诊断的共病之间的显著相互作用，这对于理解导致疾病风险的潜在机制具有重要意义。
