Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Postmus, I. et al. (2014) Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins. Nature Communications, 5(5068), (doi:10.1038/ncomms6068)

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Abstract

Statins effectively lower LDL ​cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL ​cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, ​SORT1/​CELSR2/​PSRC1 and ​SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with ​APOE and ​LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott, Professor David J and Ford, Professor Ian and Sattar, Professor Naveed
Authors: Postmus, I., Trompet, S., Deshmukh, H. A., Barnes, M. R., Li, X., Warren, H. R., Chasman, D. I., Zhou, K., Arsenault, B. J., Donnelly, L. A., Wiggins, K. L., Avery, C. L., Griffin, P., Feng, Q., Taylor, K. D., Li, G., Evans, D. S., Smith, A. V., de Keyser, C. E., Johnson, A. D., de Craen, A. J.M., Stott, D. J., Buckley, B. M., Ford, I., Westendorp, R. G. J., Eline Slagboom, P., Sattar, N., Munroe, P. B., Sever, P., Poulter, N., Stanton, A., Shields, D. C., O’Brien, E., Shaw-Hawkins, S., Ida Chen, Y.-D., Nickerson, D. A., Smith, J. D., Pierre Dubé, M., Matthijs Boekholdt, S., Kees Hovingh, G., Kastelein, J. J.P., McKeigue, P. M., Betteridge, J., Neil, A., Durrington, P. N., Doney, A., Carr, F., Morris, A., McCarthy, M. I., Groop, L., Ahlqvist, E., Bis, J. C., Rice, K., Smith, N. L., Lumley, T., Whitsel, E. A., Stürmer, T., Boerwinkle, E., Ngwa, J. S., O’Donnell, C. J., Vasan, R. S., Wei, W.-Q., Wilke, R. A., Liu, C.-T., Sun, F., Guo, X., Heckbert, S. R., Post, W., Sotoodehnia, N., Arnold, A. M., Stafford, J. M., Ding, J., Herrington, D. M., Kritchevsky, S. B., Eiriksdottir, G., Launer, L. J., Harris, T. B., Chu, A. Y., Giulianini, F., MacFadyen, J. G., Barratt, B. J., Nyberg, F., Stricker, B. H., Uitterlinden, A. G., Hofman, A., Rivadeneira, F., Emilsson, V., Franco, O. H., Ridker, P. M., Gudnason, V., Liu, Y., Denny, J. C., Ballantyne, C. M., Rotter, J. I., Adrienne Cupples, L., Psaty, B. M., Palmer, C. N.A., Tardif, J.-C., Colhoun, H. M., Hitman, G., Krauss, R. M., Wouter Jukema, J., Caulfield, M. J., Donnelly, P., Barroso, I., Blackwell, J. M., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Deloukas, P., Duncanson, A., Jankowski, J., Markus, H. S., Mathew, C. G., Palmer, C. N.A., Plomin, R., Rautanen, A., Sawcer, S. J., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C.A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Giannoulatou, E., Pirinen, M., Pearson, R., Strange, A., Su, Z., Vukcevic, D., Donnelly, P., Langford, C., Hunt, S. E., Edkins, S., Gwilliam, R., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Gray, E., Hammond, N., Jayakumar, A., McCann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Barroso, I., Deloukas, P., Mathew, C. G., Blackwell, J. M., Brown, M. A., Corvin, A., McCarthy, M. I., and Spencer, C. C.A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2014 Macmillan Publishers Limited
First Published:First published in Nature Communications 5:5068
Publisher Policy:Reproduced under a Creative Commons License
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