The CUGBP Elav-Like Family Member 4 (CELF4) gene has been highlighted recently in an earlier precursor to this meta-analysis,8 and was our top finding for convergence between functional variant prioritization and multi-tissue TWAS results (Figure 3 bottom, Supplementary File 2). This gene is important in developmental disorders, with deletions of the 18q12.2 region which encompass the gene associated with autism spectrum disorder.26 Celf4 mutant mice show aberrations in sodium channel function, perhaps through increased NAv 1.6 in the axon initial segment of excitatory neurons, and increased susceptibility to seizures.27 We agree with the assertion made in previous studies, now with additional functional and expression evidence, that CELF4 should be a focus of future brain research in depression and depression-like behaviors.
