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

Andreia Micaela Pereira, Maria Isabel Mendonca, Sofia Borges, Ana Célia Sousa, Sónia Freitas, Eva Henriques, Mariana Rodrigues, Ana Isabel Freitas, Graça Guerra, Carolina Freitas, Décio Pereira, António Brehm, Roberto Palma Dos Reis

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Pages (from-to)766-774
Number of pages9
JournalGenetics and Molecular Biology
Volume41
Issue number4
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • Coronary artery disease
  • Framingham score
  • Genetic risk score
  • Risk factors
  • Risk prediction

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