Relationship between serum uric acid and cardiovascular phenotypes in the Brisighella cohort: a Mendelian randomization analysis

Cardiovascular disease (CVD) represents the most common and lethal chronic disease worldwide. High levels of serum uric acid (SUA) have been associated with CVD and related risk factors. However, a causal link between SUA and CVD has not been proven yet. We tested the hypothesis about causal relationship between SUA levels and susceptibility to CVD using the Mendelian Randomization (MR) approach. We characterised 24 established SUA-associated DNA variants (SNPs) enriched for associations with cardiometabolic traits in a sample of 1978 individuals from the Genetics in Brisighella Heart Study (GBHS). We evaluated associations between these SNPs and SUA, creatinine, body mass index, blood pressure, coronary artery disease (CAD), hypertension (HTN) and hypercholesterolemia (HTC). We used weighted SUA-genetic risk score (GRS) based on the 5 SNPs nominally (p < 0.05) associated with SUA (rs12498742, rs2231142, rs1165151, rs1471633, rs2078267) as instrumental variable (IV) in a MR analysis of SUA levels on eight CVD-related phenotypes and compared IV estimators to SUA-trait associations from the same individuals.