(e.g. CACNA1E, CACNA1G, CACNB1, CACNG8 (Fig. 5B)), consistent with calcium signaling being altered in neurons from BD patients. Another similarity in the gene expression data were FGF14 levels: both studies show FGF14 levels are increased in BD neurons. FGF14 is a nonsecreted FGF that associates with sodium channel complexes63–66 and regulates their function along with the function of presynaptic calcium channels67. Furthermore, FGF14 localizes at the axonal initial segment (AIS) where Ankyrin G (encoded by ANK3), a BD risk gene, clusters sodium channels64,68. Lastly these FGF14/sodium channel complexes have been shown to be regulated by GSK369, a target of the BD therapeutic lithium and the inhibitor CHIR-99021 used in our study to rescue the proliferation deficit seen in BD patient NPCs. While these gene expression data suggest a functional connection between FGF14 and other BD risk associated genes, there has been to date no significant genetic association between FGF14 and bipolar disorder risk in the Psychiatric GWAS consortium’s analysis70. Nevertheless, taken together, these consistent gene expression changes and functional themes suggest that there may be several connections between genes altered in iPSC-derived BD neurons and other risk associated genes and pathways that implicate calcium signaling and AIS function as nodes
