目的·采用两样本孟德尔随机化（two-sample Mendelian randomization，TSMR）方法，以遗传变异作为工具变量，评估血浆磷脂酰乙醇胺（phosphatidylethanolamine，PE）水平与结直肠腺癌发病风险之间的因果关系。方法·PE与结直肠癌相关的单核苷酸多态性（single-nucleotide polymorphism，SNP）数据分别来自布里斯托大学MRC综合流行病学小组（The Medical Research Council Integrative Epidemiology Unit，MRC-IEU）和芬兰生物银行。对基于全基因组关联研究（genome-wide association study，GWAS）的所有汇总数据进行二次数据分析，选择与PE密切关联的遗传位点作为工具变量，采用4种孟德尔随机化（Mendelian randomization，MR）方法，包括逆方差加权法（inverse-variance weighted，IVW）、孟德尔随机化Egger回归法（Mendelian randomization-Egger，MR-Egger回归）、加权中位数法（weighted median，WME）和加权众数法（weighted mode，WM）分析评估因果效应。IVW作为主要统计方法，MR-Egger、WME和WM作为辅助方法。采用MR-Egger回归截距和MR-PRESSO检验评估水平多效性全局检验是否违反MR假设。Cochran′s Q检验用于评估异质性。结果·筛选出10个工具变量，Steiger检验显示全部PE相关SNP对结直肠癌因果关系方向一致。10个SNP中rs102275和rs9393903位点与结直肠癌风险正相关，关联度分别为0.45（P=8.01×10^-5）和0.82（P=2.31×10^-2）。4种MR分析的结果一致，均显示血浆PE水平与结直肠腺癌的发病风险存在正向关联。IVW中OR为1.36，95%CI 1.17~1.59，P=7.24×10^-5；MR-Egger回归OR为1.44，95%CI 0.97~2.14，P=1.12×10^-1；WME中OR为1.33，95%CI 1.07~1.65，P=8.81×10^-3；WM中OR为1.41，95%CI 1.12~1.77，P=1.70×10^-2。Cochran′s Q检验结果显示10个SNP对结直肠腺癌估计值无异质性。MR-Egger回归截距和MR-PRESSO检验表明全部SNP无水平多效性。采用留一法在剔除任一个SNP后，总体置信区间重叠，表明结果对单个SNP不敏感，具有较高的稳健性。结论·血浆PE水平与结直肠腺癌风险之间存在因果关联，遗传预测的血浆PE每增加1个标准差，结直肠腺癌发生风险就会增加0.36倍（95%CI 1.17~1.59，P=7.24×10^-5）。

Objective ·To employ the two-sample Mendelian randomization (TSMR) method, using genetic variants as instrumental variables, to investigate the causal relationship between phosphatidylethanolamine (PE) and the risk of colorectal adenocarcinoma. Methods ·The single-nucleotide polymorphism (SNP) data associated with PE and colorectal adenocarcinoma were obtained from the Medical Research Council Integrative Epidemiology Unit (MRC IEU) at the University of Bristol and the Finnish Biobank, respectively. A secondary data analysis was conducted using summary statistics from genome-wide association studies (GWAS), and genetic loci strongly associated with PE were selected as instrumental variables. Four Mendelian randomization (MR) methods, inverse-variance weighted (IVW) method, MR-Egger regression, weighted median (WME) method, and weighted mode (WM) method, were employed to assess the causal effect. The IVW method was used as the primary statistical approach, while MR-Egger, WME, and WM served as supplementary methods. Rigorous assessments for robustness included MR-Egger regression, MR-PRESSO global tests for horizontal pleiotropy, and Cochran′s Q test to evaluate heterogeneity. Results ·Ten instrumental variables were selected, and the Steiger test indicated that all PE-associated SNPs exhibited a consistent direction of causal effect on colorectal cancer. Among the 10 SNPs, rs102275 and rs9393903 showed the strongest positive associations with colorectal adenocarcinoma risk, with effect sizes of 0.45 (P=8.01×10^-5) and 0.82 (P=2.31×10^-2), respectively. Consistent findings from MR analyses demonstrated that PE elevated the risk of colorectal adenocarcinoma across all four methods. In the IVW analysis, the OR was 1.36 (95%CI 1.17‒1.59, P=7.24×10^-5). In the MR-Egger regression, the OR was 1.44 (95%CI 0.97‒2.14, P=1.12×10^-1). In the WEM analysis, the OR was 1.33 (95%CI 1.07‒1.65, P=8.81×10^-3). In the WM analysis, the OR was 1.41 (95%CI 1.12‒1.77, P=1.70×10^-2). Cochran′s Q test revealed no heterogeneity among the effect estimates of the 10 SNPs on colorectal adenocarcinoma. Both MR-Egger regression intercept and MR-PRESSO test indicated no evidence of horizontal pleiotropy among the SNPs. Leave-one-out analysis showed overlapping confidence intervals after excluding any single SNP, indicating that the results were not sensitive to individual SNPs and were highly robust. Conclusions ·There is a causal association between circulating PE levels and the risk of colorectal adenocarcinoma. A genetically predicted increase of one standard deviation in plasma PE levels is associated with a 1.36-fold higher risk of developing colorectal adenocarcinoma (95%CI 1.17‒1.59, P=7.24×10^-5).