Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Howson, J. M.M. et al. (2017) Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. Nature Genetics, 49(7), pp. 1113-1119. (doi: 10.1038/ng.3874) (PMID:28530674)

Abstract

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Young, Dr Robin
• Authors: Howson, J. M.M., Zhao, W., Barnes, D. R., Ho, W.-K., Young, R., Paul, D. S., Waite, L. L., Freitag, D. F., Fauman, E. B., Salfati, E. L., Sun, B. B., Eicher, J. D., Johnson, A. D., Sheu, W. H.H., Nielsen, S. F., Lin, W.-Y., Surendran, P., Malarstig, A., Wilk, J. B., Tybjærg-Hansen, A., Rasmussen, K. L., Kamstrup, P. R., Deloukas, P., Erdmann, J., Kathiresan, S., Samani, N. J., Schunkert, H., Watkins, H., Do, R., Rader, D. J., Johnson, J. A., Hazen, S. L., Quyyumi, A. A., Spertus, J. A., Pepine, C. J., Franceschini, N., Justice, A., Reiner, A. P., Buyske, S., Hindorff, L. A., Carty, C. L., North, K. E., Kooperberg, C., Boerwinkle, E., Young, K., Graff, M., Peters, U., Absher, D., Hsiung, C. A., Lee, W.-J., Taylor, K. D., Chen, Y.-H., Lee, I.-T., Guo, X., Chung, R.-H., Hung, Y.-J., Rotter, J. I., Juang, J.-M. J., Quertermous, T., Wang, T.-D., Rasheed, A., Frossard, P., Alam, D. S., Majumder, A. A. S., Di Angelantonio, E., Chowdhury, R., Chen, Y.-D. I., Nordestgaard, B. G., Assimes, T. L., Danesh, J., Butterworth, A. S., and Saleheen, D.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718
• Published Online: 22 May 2017
• Copyright Holders: Copyright © 2017 Nature America, Inc., part of Springer Nature
• First Published: First published in Nature Genetics 49(7):1113-1119
• Publisher Policy: Reproduced in accordance with the publisher copyright policy