Trans-genetic effects of circular RNA expression quantitative trait loci and potential causal mechanisms in autism [post]

Te-Lun Mai, Chia-Ying Chen, Tai-Wei Chiang, Trees-Juen Chuang
2021 unpublished
Genetic risk variants and transcriptional expression changes in autism spectrum disorder (ASD) have been widely identified, but their causal relationship is largely unknown. Circular RNAs (circRNAs) are abundant in brain and often serve as upstream regulators of mRNAs. By integrating RNA-sequencing with genotyping data from autistic brains, we accessed expression quantitative trait loci (eQTL) of circRNAs (circQTLs) that influenced expression of distant genes (trans-eGenes) and constructed
more » ... 2 circQTL-trans-eGene pairs. Mediation test suggested that 19,393 pairs were significantly cis-mediated by expression of circRNAs near the circQTLs; meanwhile, causal inference test (CIT) suggested 1,000 pairs influencing 708 trans-eGenes, wherein trans-eGene expression mediated trans-eQTL effects on ASD diagnosis. The 708 trans-eGenes were enriched for ASD risk genes and overrepresented in neurons in the upper neocortical layer. Integration of mediation test- and CIT-passing pairs further constructed 257 circQTL-circRNA-trans-eGene-ASD propagation paths. These findings increase our understanding of causative biology and cryptic regulatory mechanisms underlying ASD.
doi:10.21203/rs.3.rs-155043/v1 fatcat:46vh6g2krvatjf7puzthkx7zxq