Liu Lusha, Yin Junping, Liu Yakun, Li Bin, Kang Shan, Du Naiyi
Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Clinical Laboratory, Affiliated hospital of Hebei Engineering university, Handan, Hebei, China.
Medicine (Baltimore). 2024 Nov 22;103(47):e40690. doi: 10.1097/MD.0000000000040690.
Endometriosis (EMs) is a common gynecological disease accompanied by metabolic disturbances. However, the causality between metabolites and the risk of EMs remains unclear. We conducted a 2-sample Mendelian randomization (MR) analysis using the publicly available genome-wide association study (GWAS) of 486 circulating metabolites and EMs. The inverse variance weighted (IVW) was mainly used for assessing causality. MR-Egger intercept, MR-PRESSO Global, leave-one-out, and Cochran Q test analyses were used for sensitivity analyses. A total of 25 causal metabolites related to EMs have been identified, including 13 known and 12 unknown ones. Among the known metabolites, caffeine (OR = 0.86, 95% CI: 0.76-0.98, P = .026), cortisol (OR = 0.64, 95% CI: 0.41-0.99, P = .047), glycocholate (OR = 0.67, 95% CI: 0.51-0.87, P = .003), adrenate 22:4n6 (OR = 0.52, 95% CI: 0.35-0.77, P = .001), and ergothioneine (OR = 0.62, 95% CI: 0.47-0.81, P = .000) were protective factors for EMs, while mannose (OR = 1.43, 95% CI: 1.01-2.03, P = .044), 4-acetamidobutanoate (OR = 1.92, 95% CI: 1.27-2.89, P = .002), 1-linoleoylglycerol (OR = 1.36, 95% CI: 1.10-1.68, P = .005), bilirubin (Z, Z) (OR = 1.15, 95% CI: 1.01-1.31, P = .032), threonate (OR = 1.42, 95% CI: 1.14-1.77, P = .002), bilirubin (E, E) (OR = 1.18, 95% CI: 1.01-1.38, P = .039), erythronate (OR = 1.59, 95% CI: 1.01-2.52, P = .047), and dimethylarginine (SDMA + ADMA) (OR = 2.07, 95% CI: 1.19-3.62, P = .010) were risk factors for EMs. Additionally, there was no evidence of heterogeneity or pleiotropy of the known metabolites. Leave-one-out analysis indicated that the MR findings were robust. Our findings provide valuable circulating biomarkers as well as therapeutic targets for the screening, prevention, and treatment of EMs.
子宫内膜异位症（EMs）是一种伴有代谢紊乱的常见妇科疾病。然而，代谢物与EMs风险之间的因果关系仍不清楚。我们利用公开可得的486种循环代谢物和EMs的全基因组关联研究（GWAS）进行了两样本孟德尔随机化（MR）分析。主要采用逆方差加权（IVW）法评估因果关系。采用MR-Egger截距、MR-PRESSO全局、留一法和 Cochr an Q检验分析进行敏感性分析。共鉴定出25种与EMs相关的因果代谢物，其中13种已知，12种未知。在已知代谢物中，咖啡因（OR = 0.86，95%CI：0.76 - 0.98，P = 0.026）、皮质醇（OR = 0.64，95%CI：0.41 - 0.99，P = 0.047）、甘氨胆酸盐（OR = 0.67，95%CI：0.51 - 0.87，P = 0.003）、肾上腺酸22:4n6（OR = 0.52，95%CI：0.35 - 0.77，P = 0.001）和麦角硫因（OR = 0.62，95%CI：0.47 - 0.81，P = 0.000）是EMs的保护因素，而甘露糖（OR = 1.43，95%CI：1.01 - 2.03，P = 0.044）、4-乙酰氨基丁酸盐（OR = 1.92，95%CI：1.27 - 2.89，P = 0.002）、1-亚油酰甘油（OR = 1.36，95%CI：1.10 - 1.68，P = 0.005）、胆红素（Z，Z）（OR = 1.15，95%CI：1.01 - 1.31，P =
