Exploring the Causal Effects of Circulating ST2 and Galectin-3 on Heart Failure Risk: A Mendelian Randomization Study

Area of Science:

• Cardiovascular Science
• Genetics
• Biomarker Research

Background:

• Heart failure (HF) poses a significant global health challenge with substantial economic impact.
• Suppression of tumorigenicity 2 (ST2) and galectin-3 are recognized biomarkers for HF prognosis.
• The causal relationship between ST2, galectin-3, and HF risk requires further investigation.

Purpose of the Study:

• To investigate the potential causal relationship between genetically determined ST2 and galectin-3 levels and the risk of developing heart failure.
• To utilize Mendelian randomization to assess causality, overcoming limitations of observational studies.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) approach.
• Utilized genome-wide association study (GWAS) summary statistics for ST2, galectin-3, and HF risk.
• Applied inverse-variance weighted (IVW) analysis as the primary statistical method, supplemented by MR-Egger and leave-one-out sensitivity analyses.

Main Results:

• Four single-nucleotide polymorphisms (SNPs) for ST2 and galectin-3, respectively, served as valid instrumental variables.
• Inverse-variance weighted analysis revealed no statistically significant causal association between genetically predicted ST2 or galectin-3 and HF risk.
• Sensitivity analyses confirmed the robustness of these findings, indicating no causal link.

Conclusions:

• This Mendelian randomization study found no evidence to support a causal effect of ST2 or galectin-3 on heart failure risk.
• The findings suggest that while ST2 and galectin-3 are associated with HF prognosis, they may not be direct causal factors.