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bioRxiv · 10.1101/175844

De novo mutations involved in post-transcriptional dysregulation contribute to six neuropsychiatric disorders

Mao, F.·Wang, L.·Liu, Q.·Xiao, L.·Li, X.·He, X.·Rao, R. C.·Li, J.·Dou, Y.·Sun, Z.
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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. Here, we identified 1,736 post-transcriptionally impaired DNMs (piDNMs), and prioritized 1,482 candidate genes in four neuropsychiatric disorders from 7,748 families. Our results revealed higher prevalence of piDNMs in the probands than in controls (P = 8.19x10-17), and piDNM-harboring genes were enriched for epigenetic modifications and neuronal or synaptic functions. Moreover, we identified 86 piDNM-containing genes forming convergent co-expression modules and intensive protein-protein interactions in at least two neuropsychiatric disorders. 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 illustrate the significant contribution of piDNMs to four neuropsychiatric disorders, and lay emphasis on combining functional and network-based evidences to identify regulatory causes of genetic disorders.

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Mao, F., Wang, L., Liu, Q., Xiao, L., Li, X., He, X., Rao, R. C., Li, J., Dou, Y., Sun, Z.. 2017-08-13. De novo mutations involved in post-transcriptional dysregulation contribute to six neuropsychiatric disorders. https://doi.org/10.1101/175844

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