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A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies
- Source :
- Atherosclerosis, 223(2), 421-426. Elsevier Ireland Ltd
- Publication Year :
- 2012
- Publisher :
- Elsevier Ireland Ltd, 2012.
-
Abstract
- Objective Multiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs). Methods SNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS. Results The GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07–1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 ( Δ = 0.007; 95% CI, 0.004–0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10–1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02–1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest. Conclusion Addition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies.
- Subjects :
- Male
medicine.medical_specialty
Multivariate analysis
Coronary Disease
Kaplan-Meier Estimate
030204 cardiovascular system & hematology
Polymorphism, Single Nucleotide
Risk Assessment
White People
Article
03 medical and health sciences
0302 clinical medicine
Risk Factors
Internal medicine
medicine
Humans
Genetic Predisposition to Disease
030212 general & internal medicine
Prospective Studies
cardiovascular diseases
Prospective cohort study
Netherlands
Proportional Hazards Models
Genetics
Framingham Risk Score
Receiver operating characteristic
Models, Genetic
business.industry
Proportional hazards model
Hazard ratio
Discriminant Analysis
Middle Aged
Prognosis
Confidence interval
United States
Phenotype
ROC Curve
Area Under Curve
Multivariate Analysis
Female
Cardiology and Cardiovascular Medicine
business
Risk assessment
Subjects
Details
- ISSN :
- 18791484 and 00219150
- Volume :
- 223
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Atherosclerosis
- Accession number :
- edsair.doi.dedup.....eeb90714d1b160f4b2390e8e143765a2