Insight into genetic regulation of miRNA in mouse brain

Abstract

Backgroundmicro RNA (miRNA) are important regulators of gene expression and may influence phenotypes and disease traits. The connection between genetics and miRNA expression can be determined through expression quantitative loci (eQTL) analysis, which has been extensively used in a variety of tissues, and in both human and model organisms. miRNA play an important role in brain-related diseases, but eQTL studies of miRNA in brain tissue are limited. We aim to catalog miRNA eQTL in brain tissue using miRNA expression measured on a recombinant inbred mouse panel. Because samples were collected without any intervention or treatment (naïve), the panel allows characterization of genetic influences on miRNAs’ expression levels.We used brain RNA expression levels of 881 miRNA and 1416 genomic locations to identify miRNA eQTL. To address multiple testing, we employed permutation p-values and subsequent zero permutation p-value correction. We also investigated the underlying biology of miRNA regulation using additional analyses, including hotspot analysis to search for regions controlling multiple miRNAs, and Bayesian network analysis to identify scenarios where a miRNA mediates the association between genotype and mRNA expression. We used addiction related phenotypes to illustrate the utility of our results.ResultsThirty-eight miRNA eQTL were identified after appropriate multiple testing corrections. Ten of these miRNAs had target genes enriched for brain-related pathways and mapped to four miRNA eQTL hotspots. Bayesian network analysis revealed four biological networks relating genetic variation, miRNA expression and gene expression.ConclusionsOur extensive evaluation of miRNA eQTL provides valuable insight into the role of miRNA regulation in brain tissue. Our miRNA eQTL analysis and extended statistical exploration identifies miRNA candidates in brain for future study.

Genetic regulation and heritability of miRNA and mRNA expression link to phosphorus utilization and gut microbiome

“…Moreover, the average genomic heritability estimates were slightly higher for mRNA compared to miRNA. In addition, eQTLs of miRNAs or mRNAs in cis dominated compared to trans eQTLs in terms of number and significance, which is consistent with other studies [16,23].…”

microRNA expression levels in the nucleus accumbens correlate with morphine‐taking but not morphine‐seeking behaviour in male rats

“…In contrast, chronic morphine SA upregulated mir‐32‐5p in the NAc of male animals 1D after the last drug session (Kim et al, 2018). Indeed, a study of miRNA expression quantitative loci (eQTL) in the mouse brain identified the genomic region of mir‐32‐3p as a significant eQTL and reported that addiction pathways are enriched in mir‐32 predicted target genes, including ‘morphine addiction’ (Kordas et al, 2019). Our data demonstrate a link between NAc mir‐32‐5p levels only after 1D of abstinence, only in the absence of cue exposure, and active lever pressing on the final day of morphine SA.…”

Genetic regulation and variation of expression of miRNA and mRNA transcripts in fetal muscle tissue in the context of sex, dam and variable fetal weight

“…As in our previous study, a higher number of eQTL were identified for mRNAs than for miRNAs. Moreover, for mRNAs, cis-eQTL dominated trans-eQTL in terms of number and significance [19,21,68]. More than 300 annotated mRNA transcripts showed an eQTL effect and more than 80% were cis-eQTL.…”