After TCF4, the second most significant finding (P = 3.51×10−7) in the European replication involved POM121L2, a gene with unknown function but in a location that has previously been associated with SCZ.7 In addition to NOTCH4 and POM121L2, several other genes in the MHC region replicated. The LD between the MHC SNPs reported in Table 2 (eFigure 8) showed a complex pattern and ranged from 0 to high LD (eg, SNPs in NFKBIL1, PRRC2A, and BAG6). Many of these genes are involved in immune response, although recent evidence suggests a possible role in neuronal signaling and activity-dependent changes in synaptic connectivity.34 This finding was true for some SNPs outside the MHC as well. For example, several genes with significant findings on chromosome 19 (eg, CLC) code for proteins that belong to the galectin family, which regulates immune response.
