Third, the results also implicated developmental gene regulatory processes. For instance, the genetic findings pointed at the splicing regulator RBFOX1 (the presence of two independent genetic associations in RBFOX1 strongly suggests that it is the relevant gene). Gene set analyses implicated genes containing binding sites to the protein product of RBFOX1, and this gene set is also significantly enriched for rare exonic variation in autism and schizophrenia56,57. These analyses highlight the potential importance of splicing to generate alternative isoforms; risk for major depression may be mediated not by changes in isolated amino acids but rather by changes in the proportions of isoforms coming from a gene, given that isoforms often have markedly different biological functions68,69. These convergent results provide possible clues of a biological mechanism common to multiple severe psychiatric disorders that merits future research.
