Serum urate and pancreatitis: A bidirectional Mendelian randomization study

Pancreatitis, a significant global health concern with rising incidence, requires deeper understanding of its modifiable risk factors. This Mendelian randomization study investigated bidirectional causal relationships between serum urate levels and pancreatitis subtypes (acute pancreatitis (AP), alcohol-induced AP, chronic pancreatitis (CP), and alcohol-induced CP) using genome-wide association data from the Global Urate Genetics Consortium and FinnGen Consortium. Through rigorous selection of genetic variants as instrumental variables and application of inverse-variance-weighted methods complemented by Mendelian randomization-Egger and weighted median approaches, we identified a 28% increased AP risk per 1 mg/dL serum urate elevation (OR = 1.28, 95% CI = 1.05-1.57). No significant associations emerged for CP or alcohol-related subtypes. Reverse-direction analysis revealed no causal effects of pancreatitis on urate levels. These findings establish serum urate as a novel risk determinant for AP, highlighting its potential as a therapeutic target. Further investigations should validate these associations across diverse populations and elucidate underlying biological mechanisms.