摘要目的:探讨久坐行为与主动脉夹层患病风险之间是否存在因果关联及可能作用机制。方法:基于公开发表的全基因组关联研究数据库，进行两样本孟德尔随机化以评估久坐行为的两个主要表现，即观看电视时间、使用电脑时间与主动脉夹层患病风险的因果关系。并进行异质性、多效性、"留一法"分析，以评估本研究结论的稳健性。此外，应用生物信息学方法分析遗传工具变量所富集的基因，并行基因本体论（GO）、京都基因与基因组百科全书（KEGG）富集分析以探讨使用电脑时间与主动脉夹层间患病风险的可能机制。结果:逆方差分析结果显示观看电视时间与主动脉夹层患病风险间无因果关系，而使用电脑时间可增加主动脉夹层患病风险。使用电脑时间越长，罹患主动脉夹层风险越大（ OR= 5.16，95% CI：1.32~20.21， P=0.018）。敏感性分析结果显示依次剔除各单核苷酸多效性（SNP）后，使用电脑时间、观看电视时间与主动脉夹层患病风险间的因果关系仍稳健。水平多效性分析示本研究所纳SNP均不具有水平多效性。本研究进一步将遗传工具变量所富集的基因进行GO分析示在分子功能方面主要富集于谷胱甘肽结合及氧化还原酶活性。在细胞组分方面主要富集于γ-氨基丁酸（GABA）能突触及树突等。而生物过程方面主要富集于反突触蛋白复合物的逆行反突触信号传导及血管发育等。KEGG富集分析示基因主要富集于代谢通路等。 结论:本研究通过遗传学方法研究表明，使用电脑时间与主动脉夹层间存在显著因果关系。其可能通过影响代谢通路增加罹患主动脉夹层的风险。这提示控制使用电脑时长可能是防治主动脉夹层的重要行为干预措施。

abstractsObjective:To investigate whether there is a causal association between sedentary behavior and the risk of aortic dissection and its possible mechanism.Methods:Based on the published Genome-Wide Association Study (GWAS) database, a two-sample Mendelian randomization was performed to assess the causal relationship between the risk of aortic dissection and the time spent on two major forms of sedentary behavior (television watching time and computer using time). The analysis of heterogeneity, pleiotropy, and "leave-one-out" method were carried out to evaluate the robustness of the conclusions of this study. In addition, bioinformatics methods were also applied to analyze the genes enriched by genetic tool variables, with the Gene Ontology (GO) analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to explore possible relations between the computer using time and the risk of aortic dissection.Results:Inverse variance weighting showed no causal relationship between television watching time and the aortic dissection risk, while it revealed that computer using time could increase the risk of aortic dissection. The longer the time spent using the computer, the higher the risk of aortic dissection ( OR=5.16, 95% CI: 1.32~20.21, P=0.018). Sensitivity analysis showed that the causal association between the risk of aortic dissection and the television watching/computer using time remained robust after sequentially removing single nucleotide polymorphism (SNP). Genetic pleiotropy analysis showed that none of the SNP in this study had horizontal pleiotropy. In this study, GO analysis of the genes enriched by genetic tool variables showed that: in terms of molecular function, the genes were mainly enriched in glutathione conjugation, and oxidoreductase activity; in terms of the cellular component, they were mainly concentrated in γ-aminobutyric acid (GABA) ergic synapses, dendrites, etc. In terms of the biological process, they were mainly enriched on retrograde synaptic signaling conducted by retrograde synaptic protein complexes and vascular development, etc. And KEGG enrichment analysis showed that the genes were mainly enriched in metabolic pathways, etc. Conclusion:This study showed a significant causal relationship between computer using time and the risk of aortic dissection through genetic methods, while the previous might increase the latter by affecting metabolic pathways, suggesting that controlling computer using time would be an important behavioral intervention for the prevention and treatment of aortic dissection.