An enrichment analysis for cardiometabolic traits suggests non-random assignment of genes to microRNAs

Mustafa, R. and Ghanbari, M. and Evangelou, M. and Dehghan, A. (2018) An enrichment analysis for cardiometabolic traits suggests non-random assignment of genes to microRNAs. International Journal of Molecular Sciences, 19 (11).

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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. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type: Article
Additional Information: Export Date: 16 February 2020 Correspondence Address: Dehghan, A.; Department of Epidemiology and Biostatistics, Imperial College London, St Mary’s CampusUnited Kingdom; email:
Uncontrolled Keywords: Cardiometabolic Enrichment analysis Genome-wide association studies MicroRNAs glucose hemoglobin A1c high density lipoprotein cholesterol insulin low density lipoprotein cholesterol microRNA triacylglycerol anthropometry Article atherosclerosis body mass cardiomyopathy cardiovascular disease cholesterol blood level coronary artery disease diastolic blood pressure gene gene control gene expression gene overexpression genetic analysis genetic trait genome genome-wide association study heart failure heart infarction homeostasis model assessment human hypertension insulin release insulin sensitivity non insulin dependent diabetes mellitus obesity oral glucose tolerance test phenotype pleiotropy risk factor single nucleotide polymorphism systolic blood pressure waist hip ratio cardiac muscle gene expression regulation genetic database genetics metabolism quantitative trait Databases, Genetic Genes Genetic Pleiotropy Humans Myocardium Quantitative Trait, Heritable
Subjects: WG Cardiovascular System
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: lib2 lib2 lib2
Date Deposited: 08 May 2020 15:01
Last Modified: 08 May 2020 15:01

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