文献类型：期刊文献

中文题名：两样本孟德尔随机化分析脂质组与心房颤动的因果关联

英文题名：Causal relationship between lipidome and atrial fibrillation:two-sample Mendelian randomization analysis study

作者：魏爱军[1];代骄[1];张婷[1];王鑫[2];谢萍[3];温华知[3]

第一作者：魏爱军

机构：[1]甘肃中医药大学第一临床医学院,兰州730000;[2]兰州大学第一临床医学院,兰州73000;[3]甘肃省人民医院心内科,兰州730000

第一机构：甘肃中医药大学临床医学院

年份：2026

卷号：30

期号：2

起止页码：151

中文期刊名：中华心律失常学杂志

外文期刊名：Chinese Journal of Cardiac Arrhythmias

基金：甘肃省人民医院人才库科研启动金(RC-2025-1-8);甘肃省人民医院院内科研基金(23GSSYD-28)。

语种：中文

中文关键词：心房颤动;脂质组;逆方差加权分析法;全基因组关联研究;孟德尔随机化

外文关键词：Atrial fibrillation;Lipidome;Inverse variance weighted;Genome-wide association study;Mendelian randomization

摘要：目的探索脂质组与心房颤动(房颤)的因果关系。方法本研究采用孟德尔随机化(MR)方法,纳入总样本量为407746例、包含315074个单核苷酸多态性(SNP)的房颤全基因组关联研究(GWAS)数据,以及GeneRISK队列中7174例芬兰个体涵盖13个脂质类别、179种脂质的单变量与多变量GWAS数据。以逆方差加权分析(IVW)作为主要分析方法,探讨179种脂质与房颤之间的因果关联,并通过敏感性分析验证MR分析结果的可靠性。结果IVW分析显示,在0.05的显著性水平上,共10种脂质被鉴定为与房颤的发展有因果关系。其中,神经酰胺(d40:1)水平(OR=1.132,95%CI 1.028~1.247,P=0.011)、二酰基甘油(18:1_18:1)水平(OR=1.131,95%CI 1.005~1.272,P=0.040)、磷脂酰胆碱(16:0_0:0)水平(OR=1.137,95%CI 1.015~1.341,P=0.027)、磷脂酰胆碱(O-16:0_22:5)水平(OR=1.167,95%CI 1.015~1.341,P=0.029)、鞘磷脂(d32:1)水平(OR=1.101,95%CI 1.014~1.195,P=0.021)、三酰基甘油(50:1)水平(OR=1.116,95%CI 1.004~1.241,P=0.040)和三酰基甘油(50:2)水平(OR=1.154,95%CI 1.013~1.313,P=0.030)是房颤的危险因素。而磷脂酰胆碱(16:0_20:3)水平(OR=0.874,95%CI 0.778~0.982,P=0.023)、磷脂酰胆碱(16:0_22:4)水平(OR=0.894,95%CI 0.813~0.984,P=0.022)、磷脂酰肌醇(18:1_18:2)水平(OR=0.885,95%CI 0.793~0.988,P=0.029)与房颤存在负向因果关系。MR-Egger截距检测及Cochran's Q检验表明,IVW分析结果较为可靠。敏感度分析显示没有反向因果关系、多效性证据、异质性证据。结论神经酰胺(d40:1)等7种脂质是房颤的危险因素,而磷脂酰胆碱(16:0_20:3)等3种脂质与房颤存在负向因果关联。
Objective To explore the causal relationship between lipidome and atrial fibrillation(AF).Methods In this study,the method of Mendelian randomization(MR)was used.The genome-wide association study(GWAS)data of AF were utilized,with a total sample size of 407746 cases and a total of 315074 single nucleotide polymorphisms(SNP).The univariate and multivariate GWAS data of 179 lipidome from 13 lipids categories in 7174 Finnish individuals from the GeneRISK cohort were also included.The inverse variance weighting analysis(IVW)was used as the main analysis method to evaluate the causal relationship between 179 lipids and AF.Sensitivity analysis was conducted to test the reliability of the results of the MR analysis.Results The IVW analysis showed that,at a significance level of 0.05,a total of 10 lipids were identified as having a causal relationship with the development of AF.Among them,the levels of ceramide(d40:1)(OR=1.132,95%CI 1.028-1.247,P=0.011),diacylglycerol(18:1_18:1)(OR=1.131,95%CI 1.005-1.272,P=0.040),phosphatidylcholine(16:0_0:0)(OR=1.137,95%CI 1.015-1.341,P=0.027),phosphatidylcholine(O-16:0_22:5)(OR=1.167,95%CI 1.015-1.341,P=0.029),sphingomyelin(d32:1)(OR=1.101,95%CI 1.014-1.195,P=0.021),triacylglycerol(50:1)(OR=1.116,95%CI 1.004-1.241,P=0.040),and triacylglycerol(50:2)(OR=1.154,95%CI 1.013-1.313,P=0.030)were risk factors for AF.However,the levels of phosphatidylcholine(16:0_20:3)(OR=0.874,95%CI 0.778-0.982,P=0.023),phosphatidylcholine(16:0_22:4)(OR=0.894,95%CI 0.813-0.984,P=0.022),and phosphatidylino-sitol(18:1_18:2)(OR=0.885,95%CI 0.793-0.988,P=0.029)had a negative causal relationship with AF.The MR-Egger intercept test and Cochran's Q test indicated that the results of the IVW analysis were relatively reliable.The sensitivity analysis showed no evidence of reverse causality,pleiotropy,or heterogeneity.Conclusion Seven lipids such as ceramide(d40:1)are risk factors for AF,while 3 lipids such as phosphatidylcholine(16:0_20:3)have a negative causal association with AF.