After adjusting for age, energy intake, thyroid disease, physical activity, and BMI in model 1, the interaction between TC genotype of MC4R and CSI on depression (β = 0.39, CI = 0.12, 0.66, P = 0.004), and DASS-21 (β = 0.074, CI = 0.04, 1.44, P = 0.036) remained positive. Here, MC4R is linked to major depressive disorder.