We found that genetically determined higher circulating IL-18 levels were causally associated with a higher risk for SLE (PIVW = 0.009; OR, 1.214; 95% CI, 1.049 − 1.404) and IBD (PIVW < 0.001; OR, 1.142; 95% CI, 1.062 − 1.228), but found no significant associations of IL-18 with RA (PIVW = 0.496; OR, 1.044; 95% CI, 0.923 − 1.180), AS (PIVW = 0.021; OR, 1.181; 95% CI, 1.025 − 1.361), or psoriasis (PIVW = 0.232; OR, 1.198; 95% CI, 0.891 − 1.611). This evidence concerns the gene IL18 and systemic lupus erythematosus.