Serum uric acid levels and intracerebral hemorrhage: a two-sample Mendelian Randomization study

Previous observational studies have generated controversy regarding the correlation between serum uric acid (UA) levels and intracerebral hemorrhage (ICH), with the causal relationship remaining uncertain. To assess the potential causal relationship between serum UA levels and ICH, two-sample Mendelian randomization analysis was applied. Single-nucleotide polymorphisms (SNPs) closely associated with serum UA were retrieved from the genome-wide association study (GWAS) database, including 580,505 individuals of European descent. A total of 27 and 251 SNPs were chosen as instrumental variables. Summary data for ICH included 1935 cases and 471,578 controls. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger, weighted median, and weighted mode methods, were employed to assess the potential causal relationship between serum UA levels and ICH, with odds ratios (ORs) as effect estimates. Heterogeneity was evaluated using Cochran's Q test, and sensitivity analyses were conducted using the leave-one-out method. The IVW analysis revealed that a 1 mg/dL increase in serum UA was associated with a 16.5% higher risk of ICH (OR 1.165, 95% CI 1.01-1.34, P=0.034), while a 1 quantile increase in serum UA was associated with a 25.9% higher risk (OR 1.259, 95% CI 1.091-1.46, P=0.002). Cochran's Q test showed no evidence of heterogeneity. No horizontal pleiotropy was detected. The sensitivity analysis using the leave-one-out method supported the robustness and reliability of our results. The study reveals that elevated serum UA levels are causally linked to ICH, suggesting the potential applicability of serum UA as a biomarker for the occurrence of ICH.