mentioned already, L1CAM interactions is a subpathway of “axon guidance” that was also significantly enriched for SCZ-associated genes. The L1CAM family includes 4 structurally related proteins36 of which neurofascin (NFASC) is among our SCZ-associated genes that overlap with the L1CAM interaction reference pathway. Neurofascin has been shown to participate in neurite outgrowth and stabilization of neuronal structures, the latter particularly through interaction with ankyrins.37 This interaction was also observed in our pathway analysis (interaction between L1 and ankyrins, P = 2.78×105). Ankyrin 1, 2, and 3 (ANK1, ANK2, and ANK3) are part of our SCZ-associated genes. Ankyrins are adaptor proteins that couple membrane proteins, such as voltage-gated sodium channels, to the developing cytoskeleton.38 The observed theme of cell adhesion molecules from the KEGG (Kyoto Encyclopedia of Genes and Genomes) database (P = 5.97×10−4) replicates a previous pathway analysis of large-scale SCZ genetic studies, even to the point that we observe many of the same specific genes, including CNTNAP2 and NRXN2.39
