循环脂肪酸在介导失眠对心力衰竭影响中的作用：一项两步、两样本孟德尔随机化研究。

The Role of Circulating Fatty Acids in Mediating the Effect of Insomnia on Heart Failure: A Two-Step, Two-Sample Mendelian Randomization Study.

作者信息

Zuo Bo, Yu Binhe, Wang Pengwei, Zhang Chong, Zhao Chenhao, Sun Yujing, Ai Sizhi

机构信息

Department of Cardiology, Cardiovascular Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.

Department of Cardiology, Life Science Research Center, The First Affiliated Hospital of Xinxiang Medical University, Weihui, People's Republic of China.

出版信息

Nat Sci Sleep. 2025 Mar 4;17:391-399. doi: 10.2147/NSS.S471466. eCollection 2025.

DOI:10.2147/NSS.S471466

PMID:40060366

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11890014/

Abstract

PURPOSE

Previous studies support the causal effect of insomnia on heart failure. Fatty acid metabolism plays key roles in the occurrence and development of heart failure. It is unclear whether fatty acids play roles in the causal association between insomnia and heart failure. This study aims to investigate the mediating role of fatty acids in the association between insomnia and heart failure.

METHODS

We performed two-step, two-sample Mendelian randomization analysis by applying SNPs as genetic instruments for exposures, mediators and outcomes. Summary data obtained from genome-wide association studies for insomnia, proposed fatty acid mediators and heart failure were used in this study. The overall effect of insomnia on heart failure includes direct and indirect effects.

RESULTS

Genetically predicted insomnia has a significant causal effect on circulating total fatty acids, saturated fatty acids, monounsaturated fatty acids and omega-3 fatty acids. In addition, different circulating fatty acids have no causal effect on insomnia incidence. A significant positive correlation between genetic predicted insomnia and heart failure (OR = 1.10, 95% CI: 1.06-1.14, <0.001) was observed. Finally, we found that circulating fatty acids play a mediating role in the causal association between insomnia and heart failure. Total fatty acids, saturated fatty acids and monounsaturated fatty acids explained 3% (95% CI: 0%-7.5%), 3% (95% CI: -1.1%-7.5%), 4% (95% CI: 0%- 9.7%) of the overall effect of insomnia on heart failure, respectively.

CONCLUSION

These results support circulating fatty acids as potential mediators in the causal association between insomnia and heart failure.

摘要

目的

既往研究支持失眠对心力衰竭的因果效应。脂肪酸代谢在心力衰竭的发生和发展中起关键作用。尚不清楚脂肪酸在失眠与心力衰竭的因果关联中是否发挥作用。本研究旨在探讨脂肪酸在失眠与心力衰竭关联中的中介作用。

方法

我们通过应用单核苷酸多态性（SNPs）作为暴露、中介和结局的遗传工具，进行了两步两样本孟德尔随机化分析。本研究使用了从全基因组关联研究中获得的关于失眠、提议的脂肪酸中介物和心力衰竭的汇总数据。失眠对心力衰竭的总体效应包括直接和间接效应。

结果

基因预测的失眠对循环总脂肪酸、饱和脂肪酸、单不饱和脂肪酸和ω-3脂肪酸具有显著的因果效应。此外，不同的循环脂肪酸对失眠发生率没有因果效应。观察到基因预测的失眠与心力衰竭之间存在显著正相关（OR = 1.10，95%CI：1.06 - 1.14，<0.001）。最后，我们发现循环脂肪酸在失眠与心力衰竭的因果关联中起中介作用。总脂肪酸、饱和脂肪酸和单不饱和脂肪酸分别解释了失眠对心力衰竭总体效应的3%（95%CI：0% - 7.5%）、3%（95%CI： - 1.1% - 7.5%）、4%（95%CI：0% - 9.7%）。