We observed little variation in the IVW estimates between smoking and depression when we limited the genetic variants assessed to those related to measures of generalized inflammation, but we found evidence for an attenuation of the smoking-depression association in multivariable mendelian randomization when adjusting for IL-6 activity, suggesting that the IL-6 pathway may be at least in part responsible for the association of smoking and depression. The gene discussed is IL6; the disease is depressive disorder.