Circulating levels of cytokines and risk of cardiovascular disease: a Mendelian randomization study

Frontiers in Immunology

Immunology

Lin Liu¹  Ronghuai Zhang¹  Tao Wei¹  Wei Zhang¹  Qianwei Cui¹  Bo Liu¹  Fuqiang Liu¹  Zhanfang Zhu²  Min Wu³ 

[1] Department of Cardiology, Shaanxi Provincial People’s Hospital, Xi’an, China;Department of General Internal Medicine, Xi’an Jiaotong University Hospital, Xi’an, China;Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, China;

关键词: circulating cytokines;    cardiovascular disease;    Mendelian randomization;    cis;    European;   

DOI  :  10.3389/fimmu.2023.1175421

 received in 2023-02-27, accepted in 2023-05-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundEpidemiological studies have linked various circulating cytokines to cardiovascular disease (CVD), which however remains uncertain whether these relationships represent causality or are due to bias. To address this question, we conducted a Mendelian randomization (MR) analysis to systematically investigate the causal effects of circulating cytokine levels on CVD development.MethodsThis study leveraged the summary statistic from respective genome-wide association study (GWAS) of 47 cytokines and four types of CVD. The cis-quantitative trait locus (cis-QTL) definition, derived from a GWAS meta-analysis comprising 31,112 participants of European descent, served as instruments for cytokines. A two-sample MR design was employed, followed by comprehensive sensitivity analyses to validate the robustness of results.ResultsThe results of inverse-variance weighted method using cis-protein QTL (cis-pQTL) instruments, showed the causal effects of four cytokines (i.e., IL-1ra, MCSF, SeSelectin, SCF) on the risk of coronary artery disease (CAD). We also identified causal relationships between two cytokines (i.e., IL-2ra, IP-10) and heart failure (HF), as well as two cytokines (i.e., MCP-3, SeSelectin) and atrial fibrillation (AF), after controlling for false discovery rate (FDR). The use of cis-expression QTL (cis-eQTL) revealed additional causal associations between IL-1a, MIF and CAD, between IL-6, MIF, and HF, as well as between FGFBasic and AF. No significant sign was survived for stroke with FDR applied. Results were largely consistent across sensitivity analyses.ConclusionThe present study provides supportive evidence that genetic predisposition to levels of certain cytokines causally affects the development of specific type of CVD. These findings have important implications for the creation of novel therapeutic strategies targeting these cytokines as a means of preventing and treating CVD.

【 授权许可】

Unknown   
Copyright © 2023 Wei, Zhu, Liu, Liu, Wu, Zhang, Cui, Liu and Zhang