Association between 91 inflammatory factors combined with 1400 metabolites and ankylosing spondylitis: a two-sample Mendelian randomization study

Abstract

BACKGROUND: Ankylosing spondylitis is a chronic progressive inflammatory disease of the joints. A large amount of evidence shows that ankylosing spondylitis is closely related to inflammatory factors and metabolites. However, the causal relationship between ankylosing spondylitis and inflammatory factors and metabolites is unclear. OBJECTIVE: To evaluate potential the causal relationships between 91 inflammatory cytokines combined with 1,400 metabolites and ankylosing spondylitis using the Mendelian randomization method. METHODS: A two-sample Mendelian randomization study was performed using the Genome-wide association study (GWAS) summary statistics of 91 inflammatory cytokines (n=14,824) and 1,400 serum metabolites (n=8,299) as well as GWAS data of ankylosing spondylitis from the FinnGen R10 database (3,162 cases and 2,947,070 healthy controls) were used. Inverse variance weighted, MR-Egger, weighted median, weighted model and simple model were used to examine the causal association between inflammatory cytokines combined with metabolites and ankylosing spondylitis. Sensitivity analysis was used to test whether the results of the Mendelian randomization analysis were reliable. CONCLUSION: FGF-23 and IL-7 were positively correlated with ankylosing spondylitis while CD244 and FIt3L were negatively correlated based on causal associations. FGF-23 had potential causal relationships with 62 metabolites (p<0.05), IL-7 had potential causal relationships with 68 metabolites (p<0.05), FIt3L had potential causal relationships with 37 metabolites (p<0.05), and CD244 had potential causal relationships with 61 metabolites (p<0.05). The results suggest that CD244, FGF-23, FIt3L, IL-7 may play important roles in the pathogenesis of ankylosing spondylitis, and metabolism-related inflammatory cytokines could be important in future explorations of mechanisms and drug target selections for ankylosing spondylitis.