ABC | Volume 111, Nº1, July 2018

Original Article Pereira et al. Genes and coronary artery disease risk Arq Bras Cardiol. 2018; 111(1):50-61 Figure 1 – Distribution of the number of risk alleles by cases and controls. A logistic regression model was used to determine the coronary artery disease risk by the number of risk alleles compared to the number of reference alleles (23 alleles, in relation to the median value of the controls). Dots: regression analysis odds ratio for coronary artery disease. 0.10 0.08 0.06 0.04 0.02 0.00 Density Distribution of the number of risk alleles < = 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 > = 33 < = 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 > = 33 OR Cases Controls 12% 10% 8% 6% 4% 2% 0% 2.5 1.5 0.5 2.0 1.0 Individuals Number of risk alleles Table 2 – Distribution of multiplicative genetic risk score (MGRS) for cases and controls by quartiles and gender Variables Cases (n = 1566) Controls (n = 1322) p value MGRS 0.67 ± 0.73 0.48 ± 0.53 < 0.0001 1 st Quartile 0.18 ± 0.05 0.17 ± 0.05 < 0.0001 2 nd Quartile 0.33 ± 0.05 0.33 ± 0.05 3 th Quartile 0.52 ± 0.07 0.52 ± 0.07 4 th Quartile 1.35 ± 1.02 1.18 ± 0.88 MGRS male 0.67 ± 0.77 0.48 ± 0.44 < 0.0001 MGRS female 0.65 ± 0.58 0.51 ± 0.74 0.006 MGRS was expressed as mean ± standard deviation (SD) (using Student’s t-test). Statistical significance: p < 0.05. Two ROC curves were plotted based on the TRFs without and with the GRS (Figure 3). The first ROC curve estimated an AUC of 0.72, which increased to 0.74 when the GRS was added, revealing a better fit of the model (p < 0.0001) (Figure 3). The NRI and its p value were used to make conclusions about improvements in prediction performance gained by adding a set of biomarkers to an existing risk prediction model. The addition of GRS quartiles to TRF improved the risk classification of the models (Table 4). This new marker provided a continuous NRI of 31% (95% CI: 23.8-38.3%; p < 0.0001) with 14.6% reclassification of CAD patients and 16.4% of healthy control population (Table 4). 54