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 Boer; Brendan J. Keating; Folkert W. Asselbergs; N. Charlotte Onland-Moret

doi:10.2217/pgs.16.8

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 journal › Article (Academic Journal) › peer-review

12 Citations (Scopus)

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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 language	English
Pages (from-to)	583-591
Number of pages	9
Journal	Pharmacogenomics
Volume	17
Issue number	6
DOIs	https://doi.org/10.2217/pgs.16.8
Publication status	Published - 1 Apr 2016

Keywords

pharmacogenetics cholesterol
risk score
statin therapy

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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Future at http://www.futuremedicine.com/doi/10.2217/pgs.16.8. Please refer to any applicable terms of use of the publisher.
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Leusink, M., Maitland-Van Der Zee, A. H., Ding, B., Drenos, F., Van Iperen, E. P. A., Warren, H. R., Caulfield, M. J., Cupples, L. A., Cushman, M., Hingorani, A. D., Hoogeveen, R. C., Hovingh, G. K., Kumari, M., Lange, L. A., Munroe, P. B., Nyberg, F., Schreiner, P. J., Sivapalaratnam, S., De Bakker, P. I. W., ... Onland-Moret, N. C. (2016). A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering. Pharmacogenomics, 17(6), 583-591. https://doi.org/10.2217/pgs.16.8

@article{62693889e8df4d95acfd3694838da3c2,

title = "A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering",

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.",

keywords = "pharmacogenetics cholesterol, risk score, statin therapy",

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

year = "2016",

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doi = "10.2217/pgs.16.8",

language = "English",

volume = "17",

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Leusink, M, Maitland-Van Der Zee, AH, Ding, B, Drenos, F, Van Iperen, EPA, Warren, HR, Caulfield, MJ, Cupples, LA, Cushman, M, Hingorani, AD, Hoogeveen, RC, Hovingh, GK, Kumari, M, Lange, LA, Munroe, PB, Nyberg, F, Schreiner, PJ, Sivapalaratnam, S, De Bakker, PIW, De Boer, A, Keating, BJ, Asselbergs, FW & Onland-Moret, NC 2016, 'A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering', Pharmacogenomics, vol. 17, no. 6, pp. 583-591. https://doi.org/10.2217/pgs.16.8

TY - JOUR

T1 - A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering

AU - Leusink, Maarten

AU - Maitland-Van Der Zee, Anke H.

AU - Ding, Bo

AU - Drenos, Fotios

AU - Van Iperen, Erik P A

AU - Warren, Helen R

AU - Caulfield, Mark J.

AU - Cupples, L. Adrienne

AU - Cushman, Mary

AU - Hingorani, Aroon D.

AU - Hoogeveen, Ron C.

AU - Hovingh, G. Kees

AU - Kumari, Meena

AU - Lange, Leslie A.

AU - Munroe, Patricia B.

AU - Nyberg, Fredrik

AU - Schreiner, Pamela J.

AU - Sivapalaratnam, Suthesh

AU - De Bakker, Paul I W

AU - De Boer, Anthonius

AU - Keating, Brendan J.

AU - Asselbergs, Folkert W.

AU - Onland-Moret, N. Charlotte

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - pharmacogenetics cholesterol

KW - risk score

KW - statin therapy

UR - http://www.scopus.com/inward/record.url?scp=84966441214&partnerID=8YFLogxK

U2 - 10.2217/pgs.16.8

DO - 10.2217/pgs.16.8

M3 - Article (Academic Journal)

C2 - 27045730

AN - SCOPUS:84966441214

SN - 1462-2416

VL - 17

SP - 583

EP - 591

JO - Pharmacogenomics

JF - Pharmacogenomics

IS - 6

ER -

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

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

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