Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

Postmus, I. et al. (2016) Meta-analysis of genome-wide association studies of HDL cholesterol response to statins. Journal of Medical Genetics, 53(12), pp. 835-845. (doi: 10.1136/jmedgenet-2016-103966) (PMID:27587472)

Abstract

Background: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results: We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10−4 from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10−8) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Conclusions: Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott J, Professor David and Ford, Professor Ian and Sattar, Professor Naveed
• Authors: Postmus, I., Warren, H. R., Trompet, S., Arsenault, B. J., Avery, C. L., Bis, J. C., Chasman, D. I., de Keyser, C. E., Deshmukh, H. A., Evans, D. S., Feng, Q., Li, X., Smit, R. A.J., Smith, A. V., Sun, F., Taylor, K. D., Arnold, A. M., Barnes, M. R., Barratt, B. J., Betteridge, J., Boekholdt, S. M., Boerwinkle, E., Buckley, B. M., Chen, Y.-D. I., de Craen, A. J.M., Cummings, S. R., Denny, J. C., Dubé, M. P., Durrington, P. N., Eiriksdottir, G., Ford, I., Guo, X., Harris, T. B., Heckbert, S. R., Hofman, A., Hovingh, G. K., Kastelein, J. J.P., Launer, L. J., Liu, C.-T., Liu, Y., Lumley, T., McKeigue, P. M., Munroe, P. B., Neil, A., Nickerson, D. A., Nyberg, F., O'Brien, E., O'Donnell, C. J., Post, W., Poulter, N., Vasan, R. S., Rice, K., Rich, S. S., Rivadeneira, F., Sattar, N., Sever, P., Shaw-Hawkins, S., Shields, D. C., Slagboom, P. E., Smith, N. L., Smith, J. D., Sotoodehnia, N., Stanton, A., Stott, D. J., Stricker, B. H., Stürmer, T., Uitterlinden, A. G., Wei, W.-Q., Westendorp, R. G.J., Whitsel, E. A., Wiggins, K. L., Wilke, R. A., Ballantyne, C. M., Colhoun, H. M., Cupples, L. A., Franco, O. H., Gudnason, V., Hitman, G., Palmer, C. N.A., Psaty, B. M., Ridker, P. M., Stafford, J. M., Stein, C. M., Tardif, J.-C., Caulfield, M. J., Jukema, J. W., Rotter, J. I., and Krauss, R. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Journal of Medical Genetics
• Publisher: BMJ Publishing Group
• ISSN: 0022-2593
• ISSN (Online): 1468-6244
• Published Online: 01 September 2016
• Copyright Holders: Copyright © 2017 BMJ Publishing Group
• First Published: First published in Journal of Medical Genetics 53(12):835-845
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher.