Human blood metabolites and obesity-related asthma-a Mendelian randomization study.

Purpose: Obesity-related asthma poses serious health problems. Blood metabolite concentrations play crucial roles in its development, but the association with obesity-related asthma risk is unclear. This study aimed to explore the causal effect of blood metabolite levels on this risk.

Patients and methods: Using data from the 2023 FinnGen study, which included 345,200 subjects, with 10,306 patients having obesity-associated asthma, we conducted a two-sample Mendelian randomization (MR) analysis. We assessed the causal relationship between 1400 blood metabolites and the risk of developing obesity-associated asthma. The inverse-variance weighting (IVW) method was used to estimate the causal link, with additional tests for heterogeneity and pleiotropy to ensure robustness.

Results: The forward MR results showed that 71 metabolites were associated with the risk of developing obesity-related asthma; 57 were previously identified, and 14 were new. Among the known metabolites, 29 were linked to an increased risk, and 28 to a decreased risk. Reverse-MR results identified four metabolites related to the risk of obesity-related asthma.

Conclusion: The ratio of proline to trans-4-hydroxyproline and branched chain 14:0 dicarboxylic acid are negatively associated with the risk, while serum concentrations of X-25810 and N-acetyl-L-alanine are positively associated with the risk.