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

• Published in: Pharmacogenomics Vol. 17; no. 6; pp. 583 - 591
• Main Authors: Leusink, Maarten, Maitland-van der Zee, Anke H, Ding, Bo, Drenos, Fotios, van Iperen, Erik PA, Warren, Helen R, Caulfield, Mark J, Cupples, L Adrienne, Cushman, Mary, Hingorani, Aroon D, Hoogeveen, Ron C, Hovingh, G Kees, Kumari, Meena, Lange, Leslie A, Munroe, Patricia B, Nyberg, Fredrik, Schreiner, Pamela J, Sivapalaratnam, Suthesh, de Bakker, Paul IW, de Boer, Anthonius, Keating, Brendan J, Asselbergs, Folkert W, Onland-Moret, N Charlotte
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.04.2016
• Subjects: Adult; Aged; Apolipoprotein E; Apolipoproteins E - genetics; ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics; Blood pressure; Cardiovascular disease; Cholesterol; Cholesterol, LDL - blood; Cholesterol, LDL - genetics; Coronary vessels; Diabetes; Endocrinology and Diabetes; Endokrinologi och diabetes; Female; Genome-Wide Association Study - methods; Genomes; Genotype; Health risk assessment; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hypotheses; Lipoproteins; Male; Medical Genetics; Medicinsk genetik; Meta-analysis; Middle Aged; pharmacogenetics cholesterol; Polymorphism, Single Nucleotide - genetics; Principal components analysis; Reumatologi och inflammation; Rheumatology and Autoimmunity; Risk Factors; risk score; Single-nucleotide polymorphism; statin therapy; Statins; Studies; United Kingdom > UK; pharmacogenetics cholesterol; risk score; statin therapy
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs.16.8

To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome. 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 (three independent studies, 5314 individuals). We further assessed the effect of a GRS based on SNPs in , and . 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 ). The GRS was associated with statin response, but the small effect size (˜2% of the average low-density lipoprotein cholesterol reduction) limits applicability.