The regulatory effect of miRNAs is a heritable genetic trait in humans

 

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dc.contributor.author Geeleher, Paul en_ZA
dc.contributor.author Huang, Stephanie en_ZA
dc.contributor.author Gamazon, Eric en_ZA
dc.contributor.author Golden, Aaron en_ZA
dc.contributor.author Seoighe, Cathal en_ZA
dc.date.accessioned 2015-11-18T03:58:45Z
dc.date.available 2015-11-18T03:58:45Z
dc.date.issued 2012 en_ZA
dc.identifier.citation Geeleher, P., Huang, S. R., Gamazon, E. R., Golden, A., & Seoighe, C. (2012). The regulatory effect of miRNAs is a heritable genetic trait in humans. BMC genomics, 13(1), 383. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15081
dc.identifier.uri http://dx.doi.org/10.1186/1471-2164-13-383
dc.description.abstract BACKGROUND:microRNAs (miRNAs) have been shown to regulate the expression of a large number of genes and play key roles in many biological processes. Several previous studies have quantified the inhibitory effect of a miRNA indirectly by considering the expression levels of genes that are predicted to be targeted by the miRNA and this approach has been shown to be robust to the choice of prediction algorithm. Given a gene expression dataset, Cheng et al. defined the regulatory effect score (RE-score) of a miRNA as the difference in the gene expression rank of targets of the miRNA compared to non-targeted genes. RESULTS: Using microarray data from parent-offspring trios from the International HapMap project, we show that the RE-score of most miRNAs is correlated between parents and offspring and, thus, inter-individual variation in RE-score has a genetic component in humans. Indeed, the mean RE-score across miRNAs is correlated between parents and offspring, suggesting genetic differences in the overall efficiency of the miRNA biogenesis pathway between individuals. To explore the genetics of this quantitative trait further, we carried out a genome-wide association study of the mean RE-score separately in two HapMap populations (CEU and YRI). No genome-wide significant associations were discovered; however, a SNP rs17409624, in an intron of DROSHA, was significantly associated with mean RE-score in the CEU population following permutation-based control for multiple testing based on all SNPs mapped to the canonical miRNA biogenesis pathway; of 244 individual miRNA RE-scores assessed in the CEU, 214 were associated (p < 0.05) with rs17409624. The SNP was also nominally significantly associated (p = 0.04) with mean RE-score in the YRI population. Interestingly, the same SNP was associated with 17 (8.5% of all expressed) miRNA expression levels in the CEU. We also show here that the expression of the targets of most miRNAs is more highly correlated with global changes in miRNA regulatory effect than with the expression of the miRNA itself. CONCLUSIONS: We present evidence that miRNA regulatory effect is a heritable trait in humans and that a polymorphism of the DROSHA gene contributes to the observed inter-individual differences. en_ZA
dc.language.iso eng en_ZA
dc.publisher BioMed Central Ltd en_ZA
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_ZA
dc.source BMC Genomics en_ZA
dc.source.uri http://www.biomedcentral.com/bmcgenomics/ en_ZA
dc.subject.other microRNAs (miRNAs) en_ZA
dc.subject.other inhibitory effect en_ZA
dc.subject.other regulatory effect score (RE-score) en_ZA
dc.title The regulatory effect of miRNAs is a heritable genetic trait in humans en_ZA
dc.type Journal Article en_ZA
dc.rights.holder 2012 Geeleher et al.; licensee BioMed Central Ltd. en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Institute of Infectious Disease and Molecular Medicine en_ZA
uct.type.filetype Text
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This is an Open Access article distributed under the terms of the Creative Commons Attribution License Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License