Association of serum uric acid level with intracranial aneurysms: A Mendelian randomization study

Objective: Numerous studies have posited the involvement of serum uric acid (SUA) in the pathogenesis and progression of various cardiovascular diseases, particularly aortic aneurysms. However, the casual effect of SUA level on intracranial aneurysms (IAs) was rarely studied. Consequently, we aimed to explore the causal association between SUA and IAs using Mendelian randomization (MR) analysis. Methods: We conducted a two-sample MR analysis with SUA as the exposure variable and IAs as the outcome variable. Genome-wide association study (GWAS) datasets for SUA were acquired from the Open GWAS catalog, including 389,404 European and 129,405 East Asian individuals. The dataset for IAs was sourced from a meta-analysis of GWASs comprising 317,636 individuals across different ancestral populations (European: 7495 cases and 71,934 controls; East Asian: 3259 cases and 234,948 controls). The MR analyses were performed according to populations (European and East Asian) and IAs status [unruptured IAs (uIAs) or aneurysmal subarachnoid hemorrhage (aSAH)], respectively. The inverse variance weighted (IVW) method was employed as primary analysis to discern causal estimates. Results: Our findings revealed that an elevated genetically predicted SUA level (mg/dL) correlated with an increased risk of IAs among the European population (OR = 1.29 [95%CI:1.05-1.57], P = 0.013) and East Asian population (OR = 1.56 [95%CI: 1.27-1.92], P < 0.001). Among European individuals, subgroup analysis indicated a persistent causal association of SUA with uIAs (OR = 1.50 [95%CI: 1.08-2.08], P = 0.015) and aSAH (OR = 1.26 [95%CI: 1.00-1.60], P = 0.049). However, subgroup analysis in East Asian populations was not conducted due to the lack of separate data on uIAs and aSAH. Conclusions: Our MR analysis demonstrated a causal relationship between elevated SUA levels and an amplified risk of IAs. Further rigorous investigations are imperative to provide evidence and elucidate the underlying mechanisms.