More importantly, FAM46C, SLC7A7, LY96, CFI, DDIT4L, CD14, C5AR1 and IGJ were the most significant crosstalk genes between periodontitis and MS, and CFI, DDIT4L, FAM46C can be used as potential biomarkers for the diagnosis of periodontitis and MS. This evidence concerns the gene C5AR1 and periodontitis.