The pleiotropic effects of voltage-gated calcium channels on childhood-onset and adult-onset psychiatric disorders are underscored by pathway analysis in which calcium-channel activity genes, including our main two L-type subunit genes, showed significant enrichment in the five disorder dataset. The PGC analysis of bipolar disorder reported enrichment of a pathway including CACNA1C and CACNA1D; importantly, however, we detected enrichment of these genes after exclusion of the bipolar disorder dataset. Thus, our results suggest that voltage-gated calcium signalling, and, more broadly, calcium-channel activity, could be an important biological process in psychiatric disorders. A fourth region associated with cross-disorder effects was on chromosome 10, encompassing several genes with the peak signal in an intron of AS3MT. Loci previously associated with schizophrenia and bipolar disorder6,7 had varying evidence of association for the other major psychiatric disorders. For example, a locus previously strongly associated with schizophrenia, encompassing MIR137 and DPYD on chromosome 1, showed similar evidence of association with autism spectrum disorders; this finding is consistent with reports that autism spectrum disorders are related to microdeletions of this region.38,39
