Highlights
- •This study extends the knowledge of genetic risk of coronary artery disease in Danes.
- •A genetic risk score of 45 CAD risk-variants associate with myocardial infarction.
- •The genetic risk score improves C-index but not reclassification by European SCORE risk factors.
Abstract
Background
In Europeans, 45 genetic risk variants for coronary artery disease (CAD) have been
identified in genome-wide association studies. We constructed a genetic risk score
(GRS) of these variants to estimate the effect on incidence and clinical predictability
of myocardial infarction (MI) and CAD.
Methods
Genotype was available from 6041 Danes. An unweighted GRS was constructed by making
a summated score of the 45 known genetic CAD risk variants. Registries provided information
(mean follow-up = 11.6 years) on CAD (n = 374) and MI (n = 124) events. Cox proportional
hazard estimates with age as time scale was adjusted for sex, BMI, type 2 diabetes
mellitus and smoking status. Analyses were also stratified either by sex or median
age (below or above 45 years of age). We estimated GRS contribution to MI prediction
by assessing net reclassification index (NRI) and integrated discrimination improvement
(IDI) added to the European SCORE for 10-year MI risk prediction.
Results
The GRS associated significantly with risk of incident MI (allele-dependent hazard
ratio (95%CI): 1.06 (1.02–1.11), p = 0.01) but not with CAD (p = 0.39). Stratification revealed association of GRS with MI in men (1.06 (1.01–1.12),
p = 0.02) and in individuals above the median of 45.11 years of age (1.06 (1.00–1.12),
p = 0.03). There was no interaction between GRS and gender (p = 0.90) or age (p = 0.83). The GRS improved neither NRI nor IDI.
Conclusion
The GRS of 45 GWAS identified risk variants increase the risk of MI in a Danish cohort.
The GRS did not improve NRI or IDI beyond the performance of conventional European
SCORE risk factors.
Keywords
Abbreviations:
GRS (genetic risk score), CAD (coronary artery disease), MI (myocardial infarction), SNP (single-nucleotide polymorphism), SBP (systolic blood-pressure), DBP (diastolic blood-pressure)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: March 17, 2015
Accepted:
March 12,
2015
Received in revised form:
January 1,
2015
Received:
August 11,
2014
Identification
Copyright
© 2015 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
