Causal relationship between serum urate and asthma: a Mendelian randomization study.

Abstract

Background: Previous studies have suggested that elevated urate levels may increase the risk of asthma; however, the nature of this association remains debated. To clarify this uncertainty, we conducted a Mendelian randomization (MR) study to investigate the potential causal relationship.

Methods: Summary statistics for urate were sourced from the Global Urate Genetics Consortium (GUGC), and those for asthma were obtained from the FinnGen database. Genetic variants strongly associated with urate were selected as instrumental variables (IVs). Univariable and multivariable MR analyses were conducted to investigate the causal relationship between urate and asthma. Subsequently, network MR analyses were performed to reveal the mediating role of urate in the relationship between body mass index (BMI) and asthma.

Results: The univariable MR analysis showed that urate was associated with an increased risk of asthma (IVW OR = 1.13, 95%CI = 1.04-1.23, p = 0.004). This causal relationship remained consistent in multivariable MR analyses, even after adjusting for potential confounders, including smoking initiation, cigarettes per day, alcohol intake frequency, BMI, allergic rhinitis, and gastroesophageal reflux disease (GERD). Furthermore, network MR analyses demonstrated that the proportion of causal effect between BMI and asthma mediated by urate was 18.05% (95%CI = 6.23%-29.88%).

Conclusion: Our study confirms that serum urate is associated with an increased risk of asthma, suggesting its potential as a target for both prevention and treatment. Additionally, our findings indicate that urate partially mediates the relationship between BMI and asthma, emphasizing its role in the mechanism underlying BMI-induced asthma.