et al., 2013). Finally, a SNP within the NMDAR GRIN2A subunit gene is now genome-wide significant for schizophrenia, as are SNPs at the loci for GRIA1, GRM3 and SRR (Table 1), all of which impact on NMDAR signalling. Moreover, NMDAR signalling is critically involved in synaptic plasticity, interacting with the activity-regulated cytoskeletal protein (ARC) complex. It is thus notable that schizophrenia genes are also enriched for ARC genes (Fromer et al., 2014; Glessner et al., 2010; Lips et al., 2012; Malhotra et al., 2011; Purcell et al., 2014) and for those involved in other aspects of synaptic transmission (Kenny et al., 2014; Lips et al., 2012; Owen et al., 2005; Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). In total, there is now compelling evidence that synaptic dysfunction, particularly that related to NMDAR signalling, is one of the pathways by which the genetic predisposition to schizophrenia is mediated (Pocklington et al., 2014).
