To estimate the associations of circulating levels of cytokines with the risk of Neuromyelitis optica spectrum disorders (NMOSD).

NMOSD is a rare autoimmune disease that affects the optic nerve and spinal cord. Several studies have provided evidence of the significant involvement of the immune response in the pathogenesis of NMOSD. However, few studies have applied Mendelian randomization (MR) studies to examine the causal association between cytokines and NMOSD.

Genetic instrumental variables for circulating cytokines were identified from a genome-wide association study (GWAS) of 8293 European participants. Summary statistics of NMOSD were obtained from a GWAS including 215 NMOSD cases and 1244 controls of European ancestry. We used the inverse‑variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the simple‑median method, weighted‑median method, MR‑Egger regression, and MR pleiotropy residual sum and outlier test.

The results of the Mendelian randomization analysis revealed a statistically significant positive causal association between Macrophage inflammatory protein - 1β/CCL4 (MIP1b) and NMOSD (IVW: OR = 1.62; 95% CI: 1.05 ~ 2.48; p = 0.028). However, no significant associations were observed between the remaining cytokines and NMOSD.

Our MR analyses provided suggestive evidence to support causal associations of circulating MIP1b with the risk of NMOSD. More studies are warranted to explore how it may affect the development of NMOSD.