Genetically predicted serum uric acid and pulmonary arterial hypertension: Mendelian randomization with an exploratory NHANES risk-burden analysis
Huabin He, Zhekang Liu, Qingyun Yu, Qingan Fu, Huangxin ZhuObjective
Serum uric acid (SUA) has been associated with cardiovascular and pulmonary vascular disease, but whether SUA has a causal role in pulmonary arterial hypertension (PAH) remains uncertain. This study aimed to evaluate the genetic association between SUA and PAH using Mendelian randomization (MR), with an exploratory population-based analysis in individuals with a higher PAH-related risk-factor burden.
Methods
We conducted two-sample MR using publicly available genome-wide association study (GWAS) summary statistics. The European-ancestry SUA dataset (GCST90014015) was used as the primary exposure dataset, and a cross-population SUA dataset (GCST90018977) was used as exploratory secondary evidence. PAH outcome data were obtained from the largest available PAH GWAS. Cross-sectional NHANES 2003-2018 data were used only as descriptive exploratory context based on a PAH-related risk-factor burden.
Results
Genetically predicted SUA was associated with higher PAH risk in the European primary analysis (GCST90014015: OR=1.31, 95% CI 1.03-1.68,
Conclusion
Our study supports a positive genetic association between SUA and PAH risk. The NHANES analysis provides descriptive exploratory context in a high-risk population. Further research is needed to elucidate the underlying biological mechanisms and confirm these findings in diverse populations.