Participants with both high PRS and a history of smoking exhibited the most pronounced differential expression (18 proteins: CFHR2, SERPING1, CFHR5, CFHR4, C2, CFI, C1S, FCN2, CD46, FCN1, CR2, CLU, C4BPB, CFB, C3, CFH, CR1, CFP), suggesting the synergistic effects of genetic predisposition to AMD and smoking history in modulating complement protein expression. This evidence concerns the gene CFHR4 and age-related macular degeneration.