In conclusion, our combined analyses suggested that genetically determined plasma PPP3CA; PPP3R1, ICAM-1, cerebrospinal fluid FCG2B, SICAM-1, NID2, N-terminal pro-BNP, Layilin, and Prekallikrein levels are causally associated with SLE risk. Here, ICAM1 is linked to systemic lupus erythematosus.