Recent genome-wide association studies have pointed to single-nucleotide polymorphisms (SNPs) in genes encoding the neuronal calcium channel CaV1.2 (CACNA1C; rs1006737) and the presynaptic active zone protein Piccolo (PCLO; rs2522833) as risk factors for affective disorders, particularly major depression.
We aimed to gather more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4 with a higher association in this cohort.
These results provide further support for the involvement of the PCLO gene in MDD and show that this effect may be mediated by influencing personality traits that increase the risk of major depression.
A genome-wide association study implicated the polymorphism rs2522833 in the piccolo (PCLO) gene--involved in monoaminergic neurotransmission--as a risk factor for MDD.
Recent genetic studies showed evidence for a role of the single-nucleotide polymorphism rs2522833 within the PCLO gene in the etiology of major depression, and rs2522833 has been shown to modulate hypothalamic pituitary adrenal (HPA) axis activity during antidepressant treatment.