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

被引：0

作者：

Pereira, Andreia ^{[1
,2
]}

Mendonca, Maria Isabel ^{[1
]}

Borges, Sofia ^{[1
]}

Sousa, Ana Celia ^{[1
,2
]}

Freitas, Sonia ^{[1
]}

Henriques, Eva ^{[1
]}

Rodrigues, Mariana ^{[1
]}

Freitas, Ana Isabel ^{[1
,3
]}

Guerra, Graca ^{[1
,3
]}

Freitas, Carolina ^{[1
]}

Pereira, Decio ^{[1
]}

Brehm, Antonio ^{[3
]}

Dos Reis, Roberto Palma ^{[2
]}

机构：

[1] Hosp Dr Nelio Mendonca, Unidade Invest, Ave Luis de Camoes 57, P-9004514 Funchal, Portugal

[2] Univ Nova Lisboa, Fac Ciencias Med, Lisbon, Portugal

[3] Univ Madeira, Lab Genet Humana, Campus Univ Penteada, Madeira, Portugal

来源：

GENETICS AND MOLECULAR BIOLOGY | 2018年 / 41卷 / 04期

关键词：

Coronary artery disease; genetic risk score; Framingham score; risk prediction; risk factors; CORONARY-HEART-DISEASE; PREDICTION; SUSCEPTIBILITY; ASSOCIATION; VALIDATION; COHORT;

D O I：

10.1590/1678-4685-GMB-2017-0173

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：766 / 774

页数：9

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