Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual 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 statintreated individuals, providing a total sample size of 27 720 individuals. The only associations of genomewide 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.

doi.org/10.1136/jmedgenet-2016-103966, hdl.handle.net/1765/97286
Journal of Medical Genetics
Department of Epidemiology

Postmus, D., Warren, H., Trompet, S., Arsenault, B. J., Avery, C. L., Bis, J., … Krauss, R. (2016). Meta-analysis of genome-wide association studies of HDL cholesterol response to statins. Journal of Medical Genetics, 53(12), 835–845. doi:10.1136/jmedgenet-2016-103966