The generic neuronal system pathway in the Reactome database consists of several subpathways, such as transmission across chemical synapses, which was also among our highly significant findings. Thus, in addition to the pathways involved in neuronal growth and projection mentioned in the previous paragraphs, we observe associations with chemical neurotransmission. Among the genes in this pathway are several nicotinic acetylcholine receptors (CHRNA5, CHRNA2, and CHRNA3) that are also significant in their own subpathway (P = 2.21×10−4); voltage-gated calcium channels, such as CACNB2 and CACNB4, γ-aminobutyric acid B2 receptor (GABBR2); and a glutamate transporter (SLC1A3). Calcium signaling in particular has previously been identified as a core theme in the etiology of SCZ through large-scale genetic studies. Additional notable genes present in the transmission across chemical synapses pathway include the cyclic adenosine monophosphate response element binding protein 1 (CREB1) and the N-ethylmaleimide–sensitive factor (NSF). CREB1 is a transcription factor involved in mediating gene regulation after signaling events,40 whereas NSF is involved in vesicle trafficking and membrane fusion.41
