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The Pharmacogenetics of Statin Therapy on Clinical Events: No Evidence that Genetic Variation Affects Statin Response on Myocardial Infarction.

Trompet S, Postmus I, Warren HR et al.

35069183 PubMed ID
GWAS Study Type
12294 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

TS
Trompet S
PI
Postmus I
WH
Warren HR
NR
Noordam R
SR
Smit RAJ
TE
Theusch E
LX
Li X
AB
Arsenault B
CD
Chasman DI
HG
Hitman GA
MP
Munroe PB
RJ
Rotter JI
PB
Psaty BM
CM
Caulfield MJ
KR
Krauss RM
CA
Cupples AL
JW
Jukema WJ
Chapter II

Abstract

Summary of the research findings

The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction. Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values <5.0 × 10-4 in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI. Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p < 5.0 × 10-8). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis. Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice.

4,212 European ancestry cases, 6,557 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

12294
Total Participants
GWAS
Study Type
Yes
Replicated
180 European ancestry cases, 1,345 European ancestry controls
Replication Participants
European
Ancestry
Netherlands, Sweden, U.S., Republic of Ireland, Norway, Finland, Denmark, U.K.
Recruitment Country
Chapter IV

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