IL6R and Myalgia: Similar to IL6R perturbation39,40, IL-6 signaling downregulation through genetic perturbation in IL6 was associated with a lower risk of both polymyalgia rheumatica (odds ratio (OR) per 24% decrease in CRP of 0.76, 95% CI 0.65 to 0.89) and rheumatoid arthritis (OR of 0.87, 95% CI 0.79 to 0.95; Fig. 3d).