Related Experiment Video
Updated: Dec 3, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
The impact of growth differentiation factor 15 on the risk of cardiovascular diseases: two-sample Mendelian
Zhuo Wang1, Fangkun Yang1, Menghuai Ma1
1Department of Cardiology, Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
Background:
Growth 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.
Methods:
Genetic 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.
Results:
Among 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.
Conclusions:
The 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.
More Related Videos
Related Concept Videos
Relative Risk
Bias in Epidemiological Studies
Hazard Ratio
For example, in a clinical trial...
Confounding in Epidemiological Studies
Regression Toward the Mean
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...

