In BIP, the genome-wide significant association at CACNA1C (α subunit of the L-type voltage-gated calcium channel) deserves specific comment given its mechanistic implications. Indeed, multiple voltage gated calcium channel subunits were among the top 34 loci followed up in the BIP GWAS. Calcium channels regulate neuronal excitability (already a treatment target for BIP) and multiple brain functions including long term potentiation and synaptic plasticity. Combined analysis of the PGC BIP and SCZ samples strengthened the association in the CACNA1C region. Further, results from SGENE+ 60 implicate NRGN (neurogranin) which may act as a calcium sensor. 61 Therefore, detailed investigation of brain calcium biology is warranted for both BIP and SCZ.
