DataSheet_1_Causal association of immune cells and endometriosis: a Mendelian randomization study.pdf

ObjectiveTo investigate the causal effect of immune cells on endometriosis (EMS), we performed a Mendelian randomization analysis.
MethodsMendelian randomization (MR) uses genetic variants as instrumental variables to investigate the causal effects of exposures on outcomes in observational data. In this study, we conducted a thorough two-sample MR analysis to investigate the causal relationship between 731 immune cells and endometriosis. We used complementary Mendelian randomization (MR) methods, including weighted median estimator (WME) and inverse variance weighted (IVW), and performed sensitivity analyses to assess the robustness of our results.
ResultsFour immune phenotypes have been found to be significantly associated with the risk of developing EMS: B cell %lymphocyte (WME: OR: 1.074, p = 0.027 and IVW: OR: 1.058, p = 0.008), CD14 on Mo MDSC (WME: OR: 1.056, p =0.021 and IVW: OR: 1.047, p = 0.021), CD14+ CD16− monocyte %monocyte (WME: OR: 0.947, p = 0.024 and IVW: OR: 0.958, p = 0.011), CD25 on unsw mem (WME: OR: 1.055, p = 0.030 and IVW: OR: 1.048, p = 0.003). Sensitivity analyses confirmed the main findings, demonstrating consistency across analyses.
ConclusionsOur MR analysis provides compelling evidence for a direct causal link between immune cells and EMS, thereby advancing our understanding of the disease. It also provides new avenues and opportunities for the development of immunomodulatory therapeutic strategies in the future.

研究目的：为探究免疫细胞对子宫内膜异位症（endometriosis, EMS）的因果效应，本研究开展了孟德尔随机化（Mendelian randomization, MR）分析。
研究方法：孟德尔随机化以遗传变异作为工具变量，基于观察性数据探究暴露因素对结局的因果效应。本研究开展了全面的两样本孟德尔随机化分析，以探究731种免疫细胞与子宫内膜异位症之间的因果关联。本研究采用加权中位数估计法（weighted median estimator, WME）、逆方差加权法（inverse variance weighted, IVW）等互补的孟德尔随机化分析方法，并通过敏感性分析评估研究结果的稳健性。
研究结果：本研究发现4种免疫表型与子宫内膜异位症的发病风险存在显著关联：1. B细胞占淋巴细胞百分比（B cell %lymphocyte）：加权中位数估计法（WME）比值比（OR）=1.074，P=0.027；逆方差加权法（IVW）OR=1.058，P=0.008；2. 单核细胞源性髓系抑制细胞上的CD14分子（CD14 on Mo MDSC）：WME OR=1.056，P=0.021；IVW OR=1.047，P=0.021；3. CD14+CD16−单核细胞占单核细胞百分比（CD14+ CD16− monocyte %monocyte）：WME OR=0.947，P=0.024；IVW OR=0.958，P=0.011；4. 未转换记忆细胞上的CD25分子（CD25 on unsw mem）：WME OR=1.055，P=0.030；IVW OR=1.048，P=0.003。敏感性分析验证了核心研究结果，表明不同分析方法下结论具有一致性。
研究结论：本研究的孟德尔随机化分析为免疫细胞与子宫内膜异位症之间存在直接因果关联提供了有力证据，从而加深了我们对该疾病的认知。同时，本研究也为未来免疫调节治疗策略的开发提供了全新的思路与契机。