A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering

Maarten Leusink, Anke H. Maitland-Van Der Zee, Bo Ding, Fotios Drenos, Erik P A Van Iperen, Helen R Warren, Mark J. Caulfield, L. Adrienne Cupples, Mary Cushman, Aroon D. Hingorani, Ron C. Hoogeveen, G. Kees Hovingh, Meena Kumari, Leslie A. Lange, Patricia B. Munroe, Fredrik Nyberg, Pamela J. Schreiner, Suthesh Sivapalaratnam, Paul I W De Bakker, Anthonius De BoerBrendan J. Keating, Folkert W. Asselbergs, N. Charlotte Onland-Moret*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

7 Citations (Scopus)
239 Downloads (Pure)

Abstract

Aim: To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome.

Patients & methods:
In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin response, following up associations with p <1 × 10-4 (three independent studies, 5314 individuals). We further assessed the effect of a GRS based on SNPs in ABCG2, LPA and APOE.

Results: No new SNPs were found associated with statin response. The GRS was associated with reduced statin response: 0.0394 mmol/l per allele (95% CI: 0.0171-0.0617, p = 5.37 × 10-4).

Conclusion: The GRS was associated with statin response, but the small effect size (2% of the average low-density lipoprotein cholesterol reduction) limits applicability.
Original languageEnglish
Pages (from-to)583-591
Number of pages9
JournalPharmacogenomics
Volume17
Issue number6
DOIs
Publication statusPublished - 1 Apr 2016

Keywords

  • pharmacogenetics cholesterol
  • risk score
  • statin therapy

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