The impact of growth differentiation factor 15 on the risk of cardiovascular diseases: two-sample Mendelian randomization study

BMC Cardiovascular Disorders

Qinyi Bao¹  Menghuai Ma¹  Feiming Ye¹  Jinlian Shen¹  Zhuo Wang¹  Fangkun Yang¹  Xiaojie Xie¹ 

[1] Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, 310009, Hangzhou, Zhejiang, China;

关键词: Cardiovascular diseases;    Growth differentiation factor 15;    Mendelian randomization;    Atrial fibrillation;    Cardioembolic stroke;    Coronary artery disease;    Myocardial infarction;   

DOI  :  10.1186/s12872-020-01744-2

来源: Springer

【 摘 要 】

BackgroundGrowth differentiation factor 15 (GDF-15), a stress responsive cytokine, belongs to transforming growth factor β cytokine superfamily. Some evidence support that it’s involved in inflammation, coagulation, oxidative stress, endothelial dysfunction, and hemostasis. However, it’s still controversial whether GDF-15 directly contributes to the morbidity and mortality of patients suffered with cardiovascular disease (CVD). Besides prospective cohort study and randomized controlled trial, Mendelian randomization (MR) is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable to determine the causal relationships between exposures and health outcomes. Herein, we introduced a two-sample MR approach to evaluate the causal relationships of circulating GDF-15 levels with major CVDs incidence.MethodsGenetic instruments and summary statistics for two-sample MR analysis were obtained from 5 independent large genome-wide association studies (GWAS) to investigate the causal correlation between circulating GDF-15 levels and 9 CVDs, respectively. Conventional inverse variance weighted method was adopted to evaluate the causality of GDF-15 with different outcomes; weighted median and MR egger were used for sensitivity analyses.ResultsAmong 9 SNPs identified from 5 GWASs in 2.6 million individuals, 5 SNPs (rs1227731, rs3195944, rs17725099, rs888663, rs749451) coming from chromosome 19 and containing the PGPEP1 and GDF-15 genes were employed. Based on the instruments, circulating GDF-15 levels significantly linked to the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction. However, no significant causal association was observed for circulating GDF-15 levels with the incidence of any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy.ConclusionsThe MR study provides with genetic evidence for the causal relationship of circulating GDF-15 levels with the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction, but not any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. It indicates that GDF-15 might be a promising biomarker or potential therapeutic target for some CVDs.

【 授权许可】

CC BY