MTHFR and major depressive disorder: Indeed, although a significant association between MDD and several genes, including apolipoprotein E (APOE) (14–16), piccolo presynaptic cytomatrix protein (PCLO) (17–19), translocase of outer mitochondrial membrane 40 homolog (TOMM40) (20, 21), guanine nucleotide binding protein (G protein) beta polypeptide 3 (GNB3) (22–24), methylenetetrahydrofolate reductase (MTHFR) (25, 26), and solute carrier family 6 (neurotransmitter transporter) member 4 (SLC6A4) (27–29) have been found in several studies, a difficulty to confirm such associations in independent samples has been also reported (30–33).