An enrichment analysis for cardiometabolic traits suggests non-random assignment of genes to microRNAs
File(s)ijms-19-03666.pdf (1.08 MB)
Published version
Author(s)
Mustafa, Rima
Ghanbari, mohsen
Evangelou, marina
Dehghan, abbas
Type
Journal Article
Abstract
MicroRNAs (miRNAs) regulate the expression of 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.
Date Issued
2018-11-20
Date Acceptance
2018-11-13
Citation
International Journal of Molecular Sciences, 2018, 19 (11)
ISSN
1422-0067
Publisher
MDPI AG
Journal / Book Title
International Journal of Molecular Sciences
Volume
19
Issue
11
Copyright Statement
© 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/).
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Subjects
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
Chemistry
microRNAs
genome-wide association studies
cardiometabolic
enrichment analysis
GENOME-WIDE ASSOCIATION
METABOLIC SYNDROME
MIRNA EXPRESSION
COMMON VARIANTS
PATHOPHYSIOLOGY
METAANALYSIS
INSIGHTS
RISK
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Chemical Physics
Publication Status
Published
Article Number
ARTN 3666