Gynecology Department of Tongji Hospital, Tongji Medical-College, HUST, Wuhan, Hubei, China.
General Surgery of Tongji Hospital, Tongji Medical-College, HUST, Wuhan, Hubei, China.
PLoS One. 2024 May 31;19(5):e0301752. doi: 10.1371/journal.pone.0301752. eCollection 2024.
Prior observational research identified dyslipidemia as a risk factor for endometriosis (EMS) but the causal relationship remains unestablished due to inherent study limitations.
Genome-wide association study data for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC) from European (EUR) and East Asian (EAS) ancestries were sourced from the Global Lipids Genetics Consortium. Multi-ancestry EMS data came from various datasets. Univariable Mendelian randomization (MR) examined causal links between serum lipids and EMS. Multivariable and mediation MR explored the influence of seven confounding factors and mediators. Drug-target MR investigates the association between lipid-lowering target genes identified in positive results and EMS. The primary method was inverse-variance weighted (IVW), with replication datasets and meta-analyses reinforcing causal associations. Sensitivity analyses included false discovery rate (FDR) correction, causal analysis using summary effect estimates (CAUSE), and colocalization analysis.
IVW analysis in EUR ancestry showed a significant causal association between TG and increased EMS risk (OR = 1.112, 95% CI 1.033-1.198, P = 5.03×10-3, PFDR = 0.03), supported by replication and meta-analyses. CAUSE analysis confirmed unbiased results (P < 0.05). Multivariable and mediation MR revealed that systolic blood pressure (Mediation effect: 7.52%, P = 0.02) and total testosterone (Mediation effect: 10.79%, P = 0.01) partly mediated this relationship. No causal links were found between other lipid traits and EMS (P > 0.05 & PFDR > 0.05). In EAS ancestry, no causal relationships with EMS were detected (P > 0.05 & PFDR > 0.05). Drug-target MR indicated suggestive evidence for the influence of ANGPTL3 on EMS mediated through TG (OR = 0.798, 95% CI 0.670-0.951, P = 0.01, PFDR = 0.04, PP.H4 = 0.85%).
This MR study in EUR ancestry indicated an increased EMS risk with higher serum TG levels.
先前的观察性研究将血脂异常确定为子宫内膜异位症（EMS）的一个风险因素，但由于研究固有的局限性，这种因果关系尚未确立。
从全球脂质遗传学联盟获取了欧洲（EUR）和东亚（EAS）血统的高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、甘油三酯（TG）和总胆固醇（TC）的全基因组关联研究数据。来自不同数据集的多血统 EMS 数据。单变量孟德尔随机化（MR）检验了血清脂质与 EMS 之间的因果关系。多变量和中介物 MR 探讨了七个混杂因素和中介物的影响。药物靶向 MR 研究了在阳性结果中确定的降脂靶基因与 EMS 之间的关联。主要方法是逆方差加权（IVW），使用复制数据集和荟萃分析加强因果关联。敏感性分析包括错误发现率（FDR）校正、使用汇总效应估计值进行因果分析（CAUSE）和共定位分析。
EUR 血统的 IVW 分析显示，TG 与增加的 EMS 风险之间存在显著的因果关系（OR = 1.112，95%CI 1.033-1.198，P = 5.03×10-3，PFDR = 0.03），复制和荟萃分析支持这一结果。CAUSE 分析证实了无偏结果（P < 0.05）。多变量和中介物 MR 显示，收缩压（中介效应：7.52%，P = 0.02）和总睾酮（中介效应：10.79%，P = 0.01）部分介导了这种关系。其他脂质特征与 EMS 之间未发现因果关系（P > 0.05 和 PFDR > 0.05）。在东亚血统中，未发现与 EMS 的因果关系（P > 0.05 和 PFDR > 0.05）。药物靶向 MR 表明，ANGPTL3 通过 TG 对 EMS 的影响具有提示性证据（OR = 0.798，95%CI 0.670-0.951，P = 0.01，PFDR = 0.04，PP.H4 = 0.85%）。
这项在 EUR 血统中的 MR 研究表明，血清 TG 水平升高与 EMS 风险增加有关。
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