In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. suppl_1 ( 2017-05)
Abstract:
The most recent Genome-wide Association Study (GWAS) meta-analysis has reported a total of 58 genomic loci to be statistically significantly associated with genetic susceptibility to Coronary Artery Disease (CAD) (Consortium, 2015). Many of these loci also associate with other phenotypes, with the majority being lipid traits (Tada et al., 2014). But also hypertension, stroke (Dichgans et al., 2014) and migraine (Pickrell et al., 2016) appear to share genetic determinants with CAD. To functionally annotate the genomic loci harboring these association SNPs we sequenced the transcriptomes of 20 same donor human coronary artery endothelial (EC) and smooth muscle cell (SMC) lines. Deep RNA-Sequencing was used to assess Differential Gene Expression, Differential Splicing and Allele-Specific Expression. Focusing on GWAS loci for vascular phenotypes (CAD, stroke, migraine) we identified genes which display allele-specific differences in mRNA expression or splicing. We propose these genes as suitable targets for follow up studies. Consortium, C.A.D. (2015). A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nature genetics 47, 1121-1130. Tada, H., Won, H.H., Melander, O., Yang, J., Peloso, G.M., and Kathiresan, S. (2014). Multiple associated variants increase the heritability explained for plasma lipids and coronary artery disease. Circulation Cardiovascular genetics 7, 583-587. Dichgans, M., Malik, R., Konig, I.R., Rosand, J., Clarke, R., Gretarsdottir, S., Thorleifsson, G., Mitchell, B.D., Assimes, T.L., Levi, C., et al. (2014). Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants. Stroke; a journal of cerebral circulation 45, 24-36. Pickrell, J.K., Berisa, T., Liu, J.Z., Segurel, L., Tung, J.Y., and Hinds, D.A. (2016). Detection and interpretation of shared genetic influences on 42 human traits. Nature genetics 48, 709-717.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.37.suppl_1.447
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
1494427-3
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