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

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.
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.
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.
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.