Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.16.087395v1?rss=1 Authors: Asgari, Y., Heng, J. I.-T., Lovell, N., Forrest, A., Alinejad-Rokny, H. Abstract: Noncoding RNAs (ncRNAs) comprise a significant proportion of the mammalian genome, but their biological significance in neurodevelopment and in diseases is poorly understood. In this study, we have performed a genome-wide investigation of human noncoding RNAs for cell regulatory functions in brain tissue. By analysing ENCODE regulatory features, associations with FANTOM5 tissue-specific enhancers, as well as tissue-specific expression profiles, we have identified 17,743 noncoding RNAs comprising at least one nervous system-related expression Quantitative Trait Loci (eQTL) polymorphism that is associated with protein coding genes. Of these, 908 brain-enriched noncoding RNAs (comprising 907 long noncoding RNAs and 1 pseudogene) also overlap with chromatin states characterised as enhancers. Based on these criteria, we referred to such noncoding RNAs with putative enhancer activity as brain "enhancer-ncRNAs". To investigate their impact in neurodevelopmental disorders, we integrated GWAS SNPs and Copy Number Variation (CNV) data and found that 265 enhancer-ncRNAs were either mutated (CNV deletion or duplication) or contain at least one GWAS SNPs in the context of such conditions. Of these, the eQTL-associated gene for 82 enhancer-ncRNAs did not overlap with either GWAS SNPs or CNVs. However, in 23 of these 82 enhancer-ncRNAs, eQTL interaction was explained solely by the presence of each of these noncoding RNAs, suggesting in such contexts that mutations to neurodevelopment gene enhancers disrupt ncRNA interaction. We also cross-referenced our data with the DECIPHER database of clinical phenotypes to find that mutations to 34 of the 82 enhancer-ncRNAs are significantly associated with phenotypes including behavioural abnormality, and cognitive impairment. Taken together, we provide evidence for a distinct set of brain-enriched ncRNAs that influence genomic enhancers during neurodevelopment, suggesting enhancer mutations may be relevant to the functions for such ncRNAs in neurodevelopmental disorders. Copy rights belong to original authors. Visit the link for more info