The miRNA targetome of coronary artery disease is perturbed by functional polymorphisms identified and prioritized by in-depth bioinformatics analyses exploiting genome-wide association studies.
In recent years, genome-wide association studies (GWAS) have made great progress in elucidating the genetic influence on complex traits. An overwhelming number of GWAS signals resides in regulatory elements, therefore most post-GWAS studies focused only on transcriptional regulatory variants. However, recent findings have expanded the spectrum of trait/disease-associated regulatory variants beyond transcriptional level and highlighted the importance of post-transcriptional variants like those in miRNA targetome. The present work integrated genome-wide association data of coronary artery disease (CAD) with population-specific linkage disequilibrium structures from 1000 Genomes Project to map disease associations to miRNA targetome. Moreover, we performed a variety of functional prediction analyses to prioritize disease-associated variants (DAVs) influencing miRNA targetome and in-silico analyses to get insights into their functional significance. In conclusion, although the role of miRNA targetome variations in the development of CAD still has to be fully elucidated, we provided a systematic bioinformatics approach to the miRNA targetome variations in CAD. The results of this study will be valuable for researchers interested in the identification of CAD GWAS signals that may implicate polymorphic miRNA targeting.
Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Milad
M
Bastami
Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Ziba
Z
Nariman-Saleh-Fam
Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Zahra
Z
Saadatian
Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Lida
L
Nariman-Saleh-Fam
Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Mir Davood
MD
Omrani
Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: sghaderian@yahoo.co.uk.
Sayyed Mohammad Hossein
SMH
Ghaderian
Bambino Gesù Children's Hospital-IRCCS, Gene Expression - Microarrays Laboratory, Viale di San Paolo 15, 00146 Rome, Italy. Electronic address: andrea.masotti@opbg.net.
Andrea
A
Masotti
D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism; D030561:Databases, Nucleic Acid; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic
D035683:MicroRNAs
1000 genomes project; Coronary artery disease; Genome wide association study; Single nucleotide polymorphism; miRNA