Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
Research output: Contribution to journal › Journal article › Research › peer-review
Iris Postmus, Helen R Warren, Stella Trompet, Benoit J Arsenault, Christy L Avery, Joshua C Bis, Daniel I Chasman, Catherine E de Keyser, Harshal A Deshmukh, Daniel S Evans, QiPing Feng, Xiaohui Li, Roelof A J Smit, Albert V Smith, Fangui Sun, Kent D Taylor, Alice M Arnold, Michael R Barnes, Bryan J Barratt, John Betteridge & 68 others
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.
|Journal||Journal of Medical Genetics|
|Number of pages||11|
|Publication status||Published - Dec 2016|