摘要
目的:血脂代谢异常可能与食管癌(esophageal cancer,EC)发生相关,但其因果关系尚不明确。本研究旨在利用孟德尔随机化(Mendelian randomization,MR)方法探究血脂与EC之间的因果关系。方法:使用获取的公开全基因组关联分析(genome-wide association study,GWAS)数据,筛选合适的单核苷酸多态性(single nucleotide polymorphisms,SNPs)作为工具变量。对179种血脂(GeneRISK队列的7174例芬兰个体)与EC(196例欧洲血统病例和456080例对照)进行了双样本MR分析。采用逆方差加权(inverse-variance weighted,IVW)法作为主要的因果效应分析方法,再采用MR-Egger法、加权中位数(weighted median,WM)、简单模式和加权模式作为补充方法。采用Cochrans Q检验进行异质性检验,MR-PRESSO检验进行离群值检验并剔除离群值,MR-PRESSO检验和MR-Egger截距法进行多效性检验,“留一法”逐个剔除SNP并进行敏感性分析。结果:IVW法显示磷脂酰胆碱(O-16:1_20:4)与EC的发生呈正相关(OR=2.339,95%CI 1.573~3.479,P<0.001)。Cochran Q未检测到异质性,MR-PRESSO未检测到离群值,MR-PRESSO和MR-Egger截距法未检测到多效性,“留一法”敏感性分析表明结果具有稳健性。反向MR分析显示EC和血脂之间不存在因果关联。结论:磷脂酰胆碱(O-16:1_20:4)增加罹患EC的风险。
Objective:Abnormal lipid metabolism may be associated with the development of esophageal cancer(EC),but the causal relationship remains unclear.This study aims to explore the potential causal association between blood lipids and EC using Mendelian Randomization(MR).Methods:Publicly available genome-wide association study(GWAS)datasets were used to select appropriate single nucleotide polymorphisms(SNPs)as instrumental variables.A two-sample MR analysis was conducted using data on 179 lipid traits from the GeneRISK cohort(7174 Finnish individuals)and EC cases(196 individuals of European ancestry with 456080 controls).The inverse-variance weighted(IVW)method was used as the primary analysis to assess causal effects,supplemented by MR-Egger,weighted median(WM),simple mode,and weighted mode methods.Heterogeneity was assessed using Cochran’s Q test,outliers were identified and removed via MR-PRESSO,and pleiotropy was tested using MR-PRESSO and the MR-Egger intercept.A leave-one-out sensitivity analysis was performed to test result robustness.Results:The IVW method showed a positive causal association between phosphatidylcholine(O-16:1_20:4)and EC risk(OR=2.339,95%CI 1.573 to 3.479,P<0.001).No heterogeneity was detected by Cochran’s Q test,no outliers were identified by MR-PRESSO,and no horizontal pleiotropy was detected using the MR-PRESSO and MR-Egger intercept.The leave-one-out sensitivity analysis supported the robustness of the findings.Reverse MR analysis revealed no causal association from EC to lipid traits.Conclusion:Elevated levels of Phosphatidylcholine(O-16:1_20:4)increase the risk of EC.
作者
赵心怡
梁宇哲
刘泓娇
谭格轩
许斌
宋启斌
ZHAO Xinyi;LIANG Yuzhe;LIU Hongjiao;TAN Gexuan;XU Bin;SONG Qibin(Cancer Center,Renmin Hospital of Wuhan University,Wuhan 430060,China)
出处
《临床与病理杂志》
2025年第2期138-148,共11页
Journal of Clinical and Pathological Research
基金
国家自然科学基金(82203502)。
关键词
孟德尔随机化
脂质
磷脂酰胆碱
食管癌
全基因组关联分析
Mendelian randomization
lipids
phosphatidylcholine
esophageal cancer
genome-wide association study
