Genetic insights into blood urea nitrogen as a risk factor for coronary artery disease: a Mendelian randomization study in East Asians.

Abstract

Background: Previous studies have reported the association between blood urea nitrogen (BUN) and cardiovascular diseases (CVDs) but the causality has not yet been proved. Our study aimed to assess the causal effect of BUN levels on several CVDs using the two-sample Mendelian randomization (MR) method. This is the first MR study examining causal relationships between BUN and multiple cardiovascular diseases.

Methods: Using data from genome-wide association studies (GWAS) of East Asians, we identified single nucleotide polymorphisms (SNPs) associated with BUN levels as instrumental variables. Specifically, SNPs reaching genome-wide significance (p < 5 × 10^-8) were selected from a large-scale BUN dataset comprising (n = 148,767). To ensure robustness, multiple MR methods, including MR-Egger, weighted median, inverse variance weighting (IVW), simple mode, and weighted mode, were employed to evaluate the causal relationship between BUN levels and CVDs. Sensitivity analyses were conducted to assess the reliability and stability of the results.

Result: The IVW approach showed that a higher level of BUN was associated with an increased risk of coronary artery disease (CAD) (OR = 1.42, 95% CI = 1.226 - 1.644, p = 2.89 × 10^-6). For atrial fibrillation (OR = 0.868, 95% CI = 0.678 - 1.110, p = 0.258), arrhythmia (OR = 0.907, 95% CI = 0.777 - 1.059, p = 0.216), and congestive heart failure (OR = 0.924, 95% CI = 0.781 - 1.092, p = 0.353), no significant associations were found. Sensitivity analyses indicated the results were robust.

Conclusion: This MR work shows that elevated BUN levels are a potential biomarker for CAD risk but lack causal associations with other CVDs. These findings suggest avenues for risk stratification and CAD prevention strategies, emphasizing the clinical utility of BUN monitoring in at-risk populations.