Genetic Association of FABP4 with Cardiovascular Events: A Mendelian Randomization Study

BackgroundThere is conflicting evidence of the correlation between fatty acid binding protein 4 (FABP4) and cardiovascular disease (CVD) in previous observational studies.ObjectiveThis study aims to explore the genetic causal association between FABP4 and adverse cardiovascular (CV) events.MethodsA two-sample bidirectional Mendelian randomization (MR) analysis was performed using summary statistics from GWAS. The primary method used for MR analysis was the inverse-variance weighted (IVW) method, complemented by MR-Egger, weighted median, and weighted mode methods to explore the causal association between FABP4 and adverse CV events. For sensitivity analysis assessing heterogeneity and pleiotropy, MR-Egger and MR-PRESSO were employed to address horizontal pleiotropy, while Cochran's Q test was used to assess heterogeneity between instrumental variables (IVs). The leave-one-out analysis was used to detect outliers.ResultsIVW suggested that FABP4 showed no genetic causal effect on stroke (OR = 1.01, 95% CI = 0.98-1.04, p = 0.52), angina (OR = 1.0003, 95% CI = 0.9994-1.0012, p = 0.53), arrhythmia (OR = 1.0004, 95% CI = 0.9998-1.0009, p = 0.25), heart failure (OR = 0.99, 95% CI = 0.96-1.02, p = 0.53) or myocardial infarction (OR = 0.99, 95% CI = 0.97-1.01, p = 0.21). In the reverse MR analysis, IVW analysis showed no genetic causal effect of adverse CV events on FABP4. The results of other methods were consistent with the IVW method. Sensitivity analysis indicated the results was robust.ConclusionOur study did not find evidence to support a causal relationship between FABP4 and adverse CV events. Further studies are needed to comprehensively assess this potential association.