The most popular keywords were “mendelian randomization,” “interleukin-6,” “il-6,” “c-reactive protein,” “association,” “coronary-heart-disease,” “inflammation,” “instruments,” “risk,” “rheumatoid arthritis,” “depression.” The full extent of the existing literature over the last 10 years is systematically revealed in this study, which can provide readers with a valuable reference for fully comprehending the research hotspots and trends in the field of IL-6 signaling pathway in Mendelian randomization. The gene discussed is IL6; the disease is depressive disorder.