Abstract
While deleterious de novo mutations (DNMs) in coding region conferring risk in neuropsychiatric disorders have been revealed by next-generation sequencing, the role of DNMs involved in post-transcriptional regulation in pathogenesis of these disorders remains to be elucidated. By curating 42,871 DNMs from 9,772 core families with six kinds of neuropsychiatric disorders and controls, we identified 2,351 post-transcriptionally impaired DNMs (piDNMs) and prioritized 1,923 candidate genes in these six disorders by employing workflow RBP-Var2. Our results revealed a higher prevalence of piDNM in the probands than that of controls (P = 9.52E-17). Moreover, we identified 214 piDNM-containing genes with enriched co-expression modules and intensive protein-protein interactions (P = 7.75E-07) in at least two of neuropsychiatric disorders. Furthermore, these cross-disorder genes carrying piDNMs could form interaction network centered on RNA binding proteins, suggesting a shared post-transcriptional etiology underlying these disorders. Our findings highlight that piDNMs contribute to the pathogenesis of neuropsychiatric disorders.