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An Enrichment Analysis for Cardiometabolic Traits Suggests Non-Random Assignment of Genes to microRNAs

MicroRNAs (miRNAs) regulate the expression of the majority of genes. However, it is not known whether they regulate genes in random or are organized according to their function. To this end, we chose cardiometabolic disorders as an example and investigated whether genes associated with cardiometabol...

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Detalles Bibliográficos
Autores principales: Mustafa, Rima, Ghanbari, Mohsen, Evangelou, Marina, Dehghan, Abbas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274774/
https://www.ncbi.nlm.nih.gov/pubmed/30463316
http://dx.doi.org/10.3390/ijms19113666
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author Mustafa, Rima
Ghanbari, Mohsen
Evangelou, Marina
Dehghan, Abbas
author_facet Mustafa, Rima
Ghanbari, Mohsen
Evangelou, Marina
Dehghan, Abbas
author_sort Mustafa, Rima
collection PubMed
description MicroRNAs (miRNAs) regulate the expression of the majority of genes. However, it is not known whether they regulate genes in random or are organized according to their function. To this end, we chose cardiometabolic disorders as an example and investigated whether genes associated with cardiometabolic disorders are regulated by a random set of miRNAs or a limited number of them. Single-nucleotide polymorphisms (SNPs) reaching genome-wide level significance were retrieved from most recent genome-wide association studies on cardiometabolic traits, which were cross-referenced with Ensembl to identify related genes and combined with miRNA target prediction databases (TargetScan, miRTarBase, or miRecords) to identify miRNAs that regulate them. We retrieved 520 SNPs, of which 355 were intragenic, corresponding to 304 genes. While we found a higher proportion of genes reported from all GWAS that were predicted targets for miRNAs in comparison to all protein-coding genes (75.1%), the proportion was even higher for cardiometabolic genes (80.6%). Enrichment analysis was performed within each database. We found that cardiometabolic genes were over-represented in target genes for 29 miRNAs (based on TargetScan) and 3 miRNAs (miR-181a, miR-302d and miR-372) (based on miRecords) after Benjamini-Hochberg correction for multiple testing. Our work provides evidence for non-random assignment of genes to miRNAs and supports the idea that miRNAs regulate sets of genes that are functionally related.
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spelling pubmed-62747742018-12-15 An Enrichment Analysis for Cardiometabolic Traits Suggests Non-Random Assignment of Genes to microRNAs Mustafa, Rima Ghanbari, Mohsen Evangelou, Marina Dehghan, Abbas Int J Mol Sci Article MicroRNAs (miRNAs) regulate the expression of the majority of genes. However, it is not known whether they regulate genes in random or are organized according to their function. To this end, we chose cardiometabolic disorders as an example and investigated whether genes associated with cardiometabolic disorders are regulated by a random set of miRNAs or a limited number of them. Single-nucleotide polymorphisms (SNPs) reaching genome-wide level significance were retrieved from most recent genome-wide association studies on cardiometabolic traits, which were cross-referenced with Ensembl to identify related genes and combined with miRNA target prediction databases (TargetScan, miRTarBase, or miRecords) to identify miRNAs that regulate them. We retrieved 520 SNPs, of which 355 were intragenic, corresponding to 304 genes. While we found a higher proportion of genes reported from all GWAS that were predicted targets for miRNAs in comparison to all protein-coding genes (75.1%), the proportion was even higher for cardiometabolic genes (80.6%). Enrichment analysis was performed within each database. We found that cardiometabolic genes were over-represented in target genes for 29 miRNAs (based on TargetScan) and 3 miRNAs (miR-181a, miR-302d and miR-372) (based on miRecords) after Benjamini-Hochberg correction for multiple testing. Our work provides evidence for non-random assignment of genes to miRNAs and supports the idea that miRNAs regulate sets of genes that are functionally related. MDPI 2018-11-20 /pmc/articles/PMC6274774/ /pubmed/30463316 http://dx.doi.org/10.3390/ijms19113666 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mustafa, Rima
Ghanbari, Mohsen
Evangelou, Marina
Dehghan, Abbas
An Enrichment Analysis for Cardiometabolic Traits Suggests Non-Random Assignment of Genes to microRNAs
title An Enrichment Analysis for Cardiometabolic Traits Suggests Non-Random Assignment of Genes to microRNAs
title_full An Enrichment Analysis for Cardiometabolic Traits Suggests Non-Random Assignment of Genes to microRNAs
title_fullStr An Enrichment Analysis for Cardiometabolic Traits Suggests Non-Random Assignment of Genes to microRNAs
title_full_unstemmed An Enrichment Analysis for Cardiometabolic Traits Suggests Non-Random Assignment of Genes to microRNAs
title_short An Enrichment Analysis for Cardiometabolic Traits Suggests Non-Random Assignment of Genes to microRNAs
title_sort enrichment analysis for cardiometabolic traits suggests non-random assignment of genes to micrornas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274774/
https://www.ncbi.nlm.nih.gov/pubmed/30463316
http://dx.doi.org/10.3390/ijms19113666
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