Specifically, increased expression of HK2 in monocytes (OR = 0.96, 95% CI: 0.93-1.00, P = 0.029), NDUFS4 in both CD4+ naive T cells (OR = 0.98, 95% CI: 0.96-0.99, P = 0.002) and natural killer cells (OR = 0.97, 95% CI: 0.95-0.99, P = 0.016), and NEU1 in CD4+ naive T cells (OR = 0.86, 95% CI: 0.81-0.91, P < 0.001) were identified as protective factors against MDD. The gene discussed is HK2; the disease is major depressive disorder.