Association between circulating inflammatory cytokine levels and the risk of polymyositis: A bidirectional Mendelian randomization study

Analyses of the association between circulating inflammatory cytokine levels and polymyositis (PM) remains challenging because of the limitations of traditional observational studies. Therefore, we used Mendelian randomization (MR) to assess the causal relationship between the levels of 41 circulating inflammatory cytokines and the risk of PM. Using pooled data from genome-wide association studies (GWASs), we performed two-way MR analyses on two individual samples containing data for circulating inflammatory modulators (n = 8,186) and PM (n = 213,264) in patients of European ancestry. We used a random-effects inverse variance-weighted (IVW) method for our primary analysis and performed sensitivity and multiplicity analyses using MR-Egger, weighted-median, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran’s Q tests. The results showed that decreased circulating levels of granulocyte colony stimulating factor (GCSF) were associated with an increased risk of PM with an odds ratio (OR) of 0.31 (95% confidence interval [CI]: 0.13–0.74, p = 0.009). PM was also associated with increased circulating levels of interleukin (IL)-13 and IL-7, with OR values of 1.03 (95% CI = 1.01–1.06, p = 0.012) and 1.03 (95% CI = 1.01–1.06, p = 0.018), respectively, and decreased circulating levels of IL-1RA (OR, 0.97; 95% CI: 0.94–0.99, p = 0.040). These findings suggest that GCSF plays an important role in the pathogenesis of PM and that PM also affects the expression of the cytokines IL-13, IL-7, and IL-1RA. Further studies are required to determine whether these biomarkers can be used to prevent or treat PM.