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Conference Paper: Exploring functional variation affecting miRNA and ceRNA regulation in humans

TitleExploring functional variation affecting miRNA and ceRNA regulation in humans
Authors
Issue Date2014
Citation
The 8th Program in Quantitative Genomics (PQG) Conference, Harvard Medical School, Boston, MA., 20-21 November 2014. How to Cite?
AbstractMicroRNA (miRNA) sponges have been shown to function as competing endogenous RNAs (ceRNAs) to regulate the expression of other miRNA targets in the network by sequestering available miRNAs. As the first systematic investigation of the genome-wide genetic effect on ceRNA regulation, we applied multivariate response regression and identified widespread genetic variations that are associated with ceRNA competition using 462 Geuvadis RNA-seq data in multiple human populations. We showed that SNPs in gene 3’UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We termed these loci as endogenous miRNA sponge expression quantitative trait loci or “emsQTLs”, and found that a large number of them were unexplored in conventional eQTL mapping. We identified many emsQTLs are undergoing recent positive selection in different human populations. Using GWAS results, we found that emsQTLs are significantly enriched in traits/diseases associated loci. Functional prediction and prioritization extend our understanding on causality of emsQTL allele in disease pathways. We illustrated that emsQTL can synchronously regulate the expression of tumor suppressor and oncogene through ceRNA competition in angiogenesis. Together these results provide a distinct catalog and characterization of functional noncoding regulatory variants that control ceRNA crosstalk.
DescriptionConference Theme: Integrative Approaches to Understand Allelic Function
Persistent Identifierhttp://hdl.handle.net/10722/215596

 

DC FieldValueLanguage
dc.contributor.authorLi, MJ-
dc.contributor.authorWu, J-
dc.contributor.authorJiang, P-
dc.contributor.authorLi, W-
dc.contributor.authorZhu, Y-
dc.contributor.authorFernandez, D-
dc.contributor.authorRyan, RJH-
dc.contributor.authorChen, Y-
dc.contributor.authorWang, JJ-
dc.contributor.authorLiu, JS-
dc.contributor.authorLiu, XS-
dc.date.accessioned2015-08-21T13:31:38Z-
dc.date.available2015-08-21T13:31:38Z-
dc.date.issued2014-
dc.identifier.citationThe 8th Program in Quantitative Genomics (PQG) Conference, Harvard Medical School, Boston, MA., 20-21 November 2014.-
dc.identifier.urihttp://hdl.handle.net/10722/215596-
dc.descriptionConference Theme: Integrative Approaches to Understand Allelic Function-
dc.description.abstractMicroRNA (miRNA) sponges have been shown to function as competing endogenous RNAs (ceRNAs) to regulate the expression of other miRNA targets in the network by sequestering available miRNAs. As the first systematic investigation of the genome-wide genetic effect on ceRNA regulation, we applied multivariate response regression and identified widespread genetic variations that are associated with ceRNA competition using 462 Geuvadis RNA-seq data in multiple human populations. We showed that SNPs in gene 3’UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We termed these loci as endogenous miRNA sponge expression quantitative trait loci or “emsQTLs”, and found that a large number of them were unexplored in conventional eQTL mapping. We identified many emsQTLs are undergoing recent positive selection in different human populations. Using GWAS results, we found that emsQTLs are significantly enriched in traits/diseases associated loci. Functional prediction and prioritization extend our understanding on causality of emsQTL allele in disease pathways. We illustrated that emsQTL can synchronously regulate the expression of tumor suppressor and oncogene through ceRNA competition in angiogenesis. Together these results provide a distinct catalog and characterization of functional noncoding regulatory variants that control ceRNA crosstalk.-
dc.languageeng-
dc.relation.ispartofProgram in Quantitative Genomics (PQG) Conference-
dc.titleExploring functional variation affecting miRNA and ceRNA regulation in humans-
dc.typeConference_Paper-
dc.identifier.emailWang, JJ: junwen@hku.hk-
dc.identifier.authorityWang, JJ=rp00280-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1101/016865-
dc.identifier.hkuros247428-

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