The current study further reaffirms the genetic correlation between schizophrenia and depression observed by Wray, et al. 9. The current gene-based analysis identified the vaccinia-related kinase 2 (VRK2) gene as putatively associated with depression. Extensive research has been conducted examining the link between VRK2 and schizophrenia, with the association replicated in both European 26 and Asian 27 populations. Additionally, associations have been found between schizophrenia and the arginine and serine rich coiled-coil 1 (RSRC1) 28 and myocyte enhancer factor 2C (MEF2C) 21 genes, both of which we found to be putatively associated with depression. Hyde et al. 8 reported that RSRC1 and MEF2C were also close to the genetic variants that they detected, and they highlighted MEF2C’s role in regulation of synaptic function and central nervous system phenotypes. MEF2C was also included in ten of the 15 putative gene-sets identified for depression. The TCF4 gene coding region (Supplementary Figure 12) is also noteworthy as it contained two independently-associated variants for depression and has been identified in previous studies of depression 5, 9, 29. TCF4 is involved in the excitability of prefrontal neurons 30 and has been implicated in other psychiatric disorders, including schizophrenia 21.
