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 × 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.