Further, the functional annotation of reproducible variants of MDD susceptibility revealed 2 non-synonymous/missense variants (rs1801133/MTHFR and rs6265/BDNF) as deleterious/damaging and 6 variants (rs1800629/TNF, rs1801131/MTHFR, rs4343/ACE, rs2242446/SLC6A2, rs2273289/PLOD1, and rs41423247/NR3C1) with a score of <3 had high regulatory effect in disease condition. This evidence concerns the gene ACE and major depressive disorder.