Considering the potential impact of alcohol consumption on depression-related metabolites (45), we performed a two-step Mendelian randomization study, incorporating inflammation levels [including IL-6 (24) and CRP (25)], diet-related metabolites (28) (such as vitamin A, mannitol, and hippuric acid), acid sphingomyelinase (16), body mass index (26), and BFP (27) as mediating factors. The gene discussed is SMPD1; the disease is major depressive disorder.