Serum uric acid and pulmonary arterial hypertension: A two-sample Mendelian randomization study

Background: Observational studies have suggested a correlation between hyperuricemia and pulmonary arterial hypertension (PAH), yet the causal relationship remains uncertain. We aimed to establish this link using Mendelian Randomization (MR) methods. Objectives: Based on publicly accessible data, our study employs MR to determine the causal relationship between uric acid (UA) and PAH. Method: MR analysis was conducted among individuals of European descent. Genetic instruments linked to UA (p-value < 5 x 10(-8)) were extracted from the Chronic Kidney Disease Genetic Consortium and genome-wide association study databases. PAH risk genetic associations were sourced separately. We employed four MR methods (MR-Egger, weighted median, inverse variance weighted, and weighted mode) with selected instrumental variables to assess the causal association between UA and PAH. MR-PRESSO was used to evaluate pleiotropy and outlier Single Nucleotide Polymorphisms (SNPs), while Cochran's Q test and funnel plot assessed SNP heterogeneity. Leave-one-out analysis examined SNP impacts on causal assessment. Result: Two-sample MR analysis revealed a positive, causal relationship between UA levels and PAH. Conclusion: Our MR analysis provides robust evidence of a causal link between serum UA and PAH, suggesting UA's potential as a biomarker and therapeutic target for PAH.