A genetic risk score of 45 coronary artery disease risk variants associates with increased risk of myocardial infarction in 6041 Danish individuals
Section snippets
Background
Cardiovascular disease is the leading cause of death due to non-communicable disease and is projected to cause 23.3 million deaths globally in 2030 [1]. Cardiovascular disease includes coronary artery disease (CAD) caused by atherosclerosis of the coronary arteries, ultimately leading to myocardial infarction (MI). Several modifiable lifestyle-related risk factors such as smoking, dyslipidemia, type 2 diabetes mellitus and elevated blood pressure have been firmly established to increase the
Study samples
The Inter99 study is a randomized, non-pharmacological intervention study for the prevention of ischemic heart disease on 13,016 participants between 30 and 60 years randomly selected from the Civil Registration System. These individuals were randomized to high-intensity (90%) or low-intensity (10%) lifestyle intervention. The study was conducted at the Research Centre for Prevention and Health in Glostrup, Denmark (ClinicalTrials.gov: NCT00289237). 6784 (52%) showed up at the
Results
Table 1 shows the baseline characteristics of the Inter99 study sample. As expected, significant differences between non-cases and cases are evident for all metabolic traits. The SNPs used in the GRS are listed in Supplementary Table 1. Correlation coefficients are presented in Supplementary Table 2.
Discussion
The present study includes 45 known CAD risk variants and found an allele- and tertile-dependent increase in risk of incident MI in a prospective Danish study sample. We did not observe association with CAD risk although we had more cases than for MI. Our analyses of clinical predictive capacity did not reveal improved reclassification of MI cases and non-cases for the GRS.
Acknowledgments
We thank A. Forman, T. Lorentzen, B. Andreasen and G.J. Klavsen for technical assistance and A.L. Nielsen, G. Lademann and M.M.H. Kristensen for management assistance. The study was supported by grants from The Lundbeck Foundation Center for Applied Medical Genomics in Personalized Disease Prediction, Prevention and Care (LuCamp; http://www.lucamp.org) and The Novo Nordisk Foundation Center for Basic Metabolic Research, which is an independent research center at the University of Copenhagen
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