Among these genes, five were significant in the brain: NEGR1, LRFN5, KCL1, TMEM33 (upregulation), and SLC30A9 (downregulation), and three were annotated as druggable: NEGR1, LRFN5, and ESR2. NEGR1 is positively associated with MDD in the putamen (Z = 7.06, P = 1.67 × 10−12), LRFN5 in the cerebellum (Z = 5.21, P = 2.01 × 10−11) and cerebellar hemisphere (Z = 5.23, P = 1.68 × 10−7), whereas ESR2 is not significantly associated with MDD in the brain (cerebellum: Z = −1.73, P = 0.0843) but exhibits significant negative association in whole blood (Z = −5.43, P = 5.66 × 10−8). Here, ESR2 is linked to major depressive disorder.