Calcium signalling is emerging as another genetic convergence. CACNA1C, which encodes the L-type calcium channel Cav1.2 α subunit, was first shown to be genome-wide significant for bipolar disorder (see Bhat et al., 2012). It was subsequently shown to also be a GWAS hit across several disorders (Cross Disorder Group of the Psychiatric Genomics Consortium, 2013a) and significant for schizophrenia alone, along with CACNB2 (encoding the Cavβ2 subunit) and other genes involved in calcium regulation (Ripke et al., 2013; Schizophrenia Working Group of the Psychiatric Genomics Consortium, 2014). These genes also contain an excess of rare variants in schizophrenia (Purcell et al., 2014). Abnormalities of calcium signalling were already well documented in bipolar disorder (Casamassima et al., 2010), but involvement in schizophrenia was perhaps less anticipated. Of note, calcium signalling (Berridge, 2014), including L-type calcium channels, are integral to many aspects of synaptic plasticity, key signalling cascades, and cognition (Heck et al., 2014; Moosmang et al., 2005; White et al., 2008).
