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A Genetic Risk Score Is Associated With Incident Cardiovascular Disease and Coronary Artery CalciumClinical Perspective
G Thanassoulis, GM Peloso, MJ Pencina... - Circulation: ..., 2012 - Am Heart Assoc From the Division of Cardiology and Clinical Epidemiology, Mc Gill University Health Center and
Mc Gill University, Montreal, Quebec, Canada (GT); National Heart, Lung and Blood Institute
(NHLBI) of the National Institutes of Health (NIH) Framingham Heart Study, Framingham, ...
Methods and Results—By using findings from recent genome-wide association studies, we constructed GR Ss composed of 13 genetic variants associated with myocardial infarction or other manifestations of coronary heart disease (CHD) and 102 genetic variants associated with CHD or its major risk factors. We also updated the 13 single-nucleotide polymorphism (SNP) GR Ss with 16 SN Ps recently discovered by genome-wide association studies. We estimated the association, discrimination, and risk reclassification of each GRS for incident cardiovascular events and prevalent coronary artery calcium (CAC). In analyses adjusted for age, sex, CVD risk factors, and parental history of CVD, the 13 SNP GR Ss were significantly associated with incident hard CHD (hazard ratio, 1.07; 95% CI, 1.00–1.15; P=0.04), CVD (hazard ratio per allele, 1.05; 95% CI, 1.01–1.09; P=0.03), and high CAC (defined as >75th age- and sex-specific percentile; odds ratio per allele, 1.18; 95% CI, 1.11–1.26; P=3.4×10−7). The GRS did not improve discrimination for incident CHD or CVD but led to modest improvements in risk reclassification. However, significant improvements in discrimination and risk reclassification were observed for the prediction of high CAC. The addition of 16 newly discovered SN Ps to the 13 SNP GR Ss did not significantly modify these results.
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A Genetic Risk Score Is Associated With Incident Cardiovascular Disease and Coronary Artery CalciumClinical Perspective |
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