Genetic regulation of lncRNA expression in whole human brain and their contribution to CNS disorders

Long non-coding RNAs (lncRNAs) play a key role in the human brain, and genetic variants regulate their expression. Herein, expression quantitative trait loci of lncRNAs encompassing 10 brain regions from 134 individuals were analyzed, and novel variants influencing lncRNA expression (eSNPs) and respective affected lncRNAs (elncRNAs) were identified. The eSNPs showed proximity to their corresponding elncRNAs, enriched in the non-coding genome, and have a high minor allele frequency. The elncRNAs exhibit a high-level and complex pattern of expression. The genetic regulation is more tissue specific for lncRNAs than for protein-coding genes, with notable differences between cerebrum and cerebellum. Nonetheless, it shows relatively similar patterns across cortex regions. Furthermore, we observed a significant enrichment of eSNPs among variants associated with neurological disorders, especially insomnia, and identified insomnia-related lncRNAs involved in immune response functions. Moreover, the present study offers an improved tool for lncRNA quantification, a novel approach for lncRNA function analysis, and a database of lncRNA expression regulation in human brain. These findings and resources will advance the research on non-coding gene expression regulation in neuroscience.