脂质体与肾透明细胞癌的遗传关系：一项两样本孟德尔随机化研究

Genetic Relationship between Lipidomes and Clear Cell Renal Cell Carcinoma: Two-Sample Mendelian Randomization Study

摘要: 目的：现有研究表明，脂质体水平与肾透明细胞癌(Clear Cell Renal Cell Carcinoma, ccRCC)之间存在相关性。然而，对于脂质体与肾透明细胞癌之间的因果关系，现有文献尚未达成一致意见。本研究采用两样本孟德尔随机化(Mendelian Randomization, MR)分析来严格评估两者之间的因果关系。方法：采用可公开获取的全基因组关联研究(GWSA)数据库进行MR分析。本研究的中心方法是逆方差加权(Inverse-Variance Weighting, IVW)荟萃分析，同时联合贝叶斯加权孟德尔随机化(Bayesian Weighted Mendelian Randomization, BWMR)进一步验证结果，Cochran’s Q和MR-Egger等方法进行补充研究。结果：在MR结合BWMR分析中，发现8个与ccRCC具有直接因果关联的脂质体。卵磷脂O-18:2_16:0 (OR: 0.766, 95%CI: 0.605~0.970, p = 0.027)降低ccRCC发病风险；卵磷脂16:0_0:0 (OR: 1.231, 95%CI: 1.002~1.514, p = 0.048)、卵磷脂18:1_18:3 (OR: 1.609, 95%CI: 1.117~2.318, p = 0.011)、卵磷脂O-16:0_20:4 (OR: 1.188, 95%CI: 1.013~1.393, p = 0.034)、脑磷脂16:0_20:4 (OR: 1.173, 95%CI: 1.020~1.348, p = 0.025)、脑磷脂18:0_20:4 (OR: 1.359, 95%CI: 1.149~1.608, p = 0.001)、甘油三酯48:1 (OR: 1.259, 95%CI: 1.002~1.523, p = 0.048)及甘油三酯48:2 (OR: 1.292, 95%CI: 1.033~1.615, p = 0.025)增加ccRCC患病风险。结论：基因预测结果显示脂质体与肾透明细胞癌之间存在遗传因果关系，这为未来更多的临床研究提供了理论支持和基础。

Abstract: Objective: Existing studies suggest an association between lipidomes levels and clear cell renal cell carcinoma (ccRCC). However,consensus regarding the causal relationship between lipidomes and ccRCC has not been reached in current literature. This study aimed to rigorously assess the causal relationship between lipidome levels and ccRCC using Mendelian randomization (MR) analysis with two independent samples. Methods: Mendelian randomization analysis was conducted using publicly available genome-wide association study (GWSA) databases. The central method employed was inverse-variance weighting(IVW)meta-analysis, supplemented by Bayesian weighted Mendelian randomization(BWMR)to further validate the results, along with methods such as Cochran’s Q and MR-Egger. Results: In the MR combined with BWMR analysis, eight lipidomes traits were found to have a direct causal association with ccRCC. Decreased levels of phosphatidylcholine O-18:2_16:0 (OR: 0.766, 95%CI: 0.605~0.970, p = 0.027) were associated with a reduced risk of ccRCC. Increased risk of ccRCC was associated with phosphatidylcholine 16:0_0:0 (OR: 1.231, 95%CI: 1.002~1.514, p = 0.048), phosphatidylcholine 18:1_18:3 (OR: 1.609, 95%CI: 1.117~2.318, p = 0.011), phosphatidylcholine O-16:0_20:4 (OR: 1.188, 95%CI: 1.013~1.393, p = 0.034), phosphatidylethanolamine 16:0_20:4 (OR: 1.173, 95%CI: 1.020~1.348, p = 0.025), phosphatidylethanolamine 18:0_20:4 (OR:1.359, 95%CI:1.149~1.608, p = 0.001), triglyceride 48:1 (OR: 1.259, 95%CI: 1.002~1.523, p = 0.048), and triglyceride 48:2 (OR: 1.292, 95%CI: 1.033~1.615, p = 0.025). Conclusion: Genetic prediction indicates a causal relationship between lipidome levels and ccRCC, providing theoretical support and a basis for future clinical research.