After correction for multiple testing (appendix pp 14–16), we noted significant enrichment for a set of calcium channel activity genes associated with catalysis of facilitated diffusion of calcium ions through a trans membrane calcium channel (appendix p 64). With a cutoff of p<10−3, 20 of 67 gene regions in this set were associated in the five-disorder meta-analysis, including voltage-gated calcium-channel subunits CACNA1C, CACNA1D, CACNA1E, CACNA1S, CACNA2D2, CACNA2D4, and CACNB2 (appendix pp 65–66). Because calcium-channel genes (mainly CACNA1C) have previously been associated with bipolar disorder, we repeated the pathway analysis with exclusion of the datasets for bipolar disorder and confirmed that enrichment was not dependent on cases with this disorder (data not shown). Appendix pp 69–70 depict functional associations between these calcium-channel activity genes on the basis of various lines of evidence.
