Additional value of a combined genetic risk score to standard cardiovascular stratification

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 co...

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Published in:Genetics and molecular biology 2018-10, Vol.41 (4), p.766-774
Main Authors: Pereira, Andreia, Mendonca, Maria Isabel, Borges, Sofia, Sousa, Ana Célia, Freitas, Sónia, Henriques, Eva, Rodrigues, Mariana, Freitas, Ana Isabel, Guerra, Graça, Freitas, Carolina, Pereira, Décio, Brehm, António, Reis, Roberto Palma Dos
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Language:English
Subjects:
BIOCHEMISTRY & MOLECULAR BIOLOGY
Cardiovascular disease
Cardiovascular diseases
Coronary artery
Coronary artery disease
Diabetes mellitus
Dyslipidemia
Framingham score
Genetic diversity
genetic risk score
Genetic variance
GENETICS & HEREDITY
Genotyping
Health risk assessment
Health risks
Heart diseases
Human and Medical Genetics
Hypertension
Multivariate analysis
Predictions
Reclassification
Regression analysis
Risk
risk factors
risk prediction
Smoking
Subgroups
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creator Pereira, Andreia
Mendonca, Maria Isabel
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Guerra, Graça
Freitas, Carolina
Pereira, Décio
Brehm, António
Reis, Roberto Palma Dos
description 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
doi_str_mv 10.1590/1678-4685-GMB-2017-0173
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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&lt;0.0001). Diabetes, arterial hypertension, dyslipidemia and smoking status were also independent CAD predictors (p&lt;0.05). GRS added predictive value to TRF across all risk subgroups. 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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.</abstract><cop>Brazil</cop><pub>Sociedade Brasileira de Genetica</pub><pmid>30571812</pmid><doi>10.1590/1678-4685-GMB-2017-0173</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects BIOCHEMISTRY & MOLECULAR BIOLOGY
Cardiovascular disease
Cardiovascular diseases
Coronary artery
Coronary artery disease
Diabetes mellitus
Dyslipidemia
Framingham score
Genetic diversity
genetic risk score
Genetic variance
GENETICS & HEREDITY
Genotyping
Health risk assessment
Health risks
Heart diseases
Human and Medical Genetics
Hypertension
Multivariate analysis
Predictions
Reclassification
Regression analysis
Risk
risk factors
risk prediction
Smoking
Subgroups
title Additional value of a combined genetic risk score to standard cardiovascular stratification
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