Key result
A multi-locus genetic risk score was an independent predictor for coronary artery disease (OR 1.87; p<0.0001) and provided incremental predictive value, especially in the intermediate risk subgroup.
Why the study?
The utility of genetic risk scores as independent risk predictors remains inconclusive.
Does a multi-locus genetic risk score (GRS) improve coronary artery disease risk prediction when added to the Framingham risk score in individuals?
Case-Control (n=2,888)
Does a multi-locus genetic risk score (GRS) improve coronary artery disease risk prediction when added to the Framingham risk score in individuals?
Odds Ratio: 1.87
p-value: p=<0.0001
Adding a 32-variant genetic risk score to the Framingham risk score significantly improves coronary artery disease risk stratification, particularly for patients at intermediate risk.
Supports GRS for CAD reclassification in intermediate risk; leaves open prospective validation before clinical use.
The utility of genetic risk scores (GRS) as independent risk predictors remains inconclusive. Here, we evaluate the additive value of a multi-locus GRS to the Framingham risk score (FRS) in coronary artery disease (CAD) risk prediction. A total of 2888 individuals (1566 coronary patients and 1322 controls) were divided into three subgroups according to FRS. Multiplicative GRS was determined for 32 genetic variants associated to CAD. Logistic Regression and Area Under the Curve (AUC) were determined first, using the TRF for each FRS subgroup, and secondly, adding GRS. Different models (TRF, TRF+GRS) were used to classify the subjects into risk categories for the FRS 10-year predicted risk. The improvement offered by GRS was expressed as Net Reclassification Index and Integrated Discrimination Improvement. Multivariate analysis showed that GRS was an independent predictor for CAD (OR = 1.87; p<0.0001). Diabetes, arterial hypertension, dyslipidemia and smoking status were also independent CAD predictors (p<0.05). GRS added predictive value to TRF across all risk subgroups. NRI showed a significant improvement in all categories. In conclusion, GRS provided a better incremental value in intermediate subgroup. In this subgroup, inclusion of genotyping may be considered to better stratify cardiovascular risk.
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Pereira et al. (2018) conducted a case-control in Coronary artery disease (n=2,888). Multi-locus genetic risk score (GRS) vs. Framingham risk score (FRS) / Traditional risk factors was evaluated on Coronary artery disease (CAD) (OR 1.87, p=<0.0001). A multi-locus genetic risk score was an independent predictor for coronary artery disease (OR 1.87; p<0.0001) and provided incremental predictive value, especially in the intermediate risk subgroup.