Descriptive and comparative analysis

Continuous variables were defined as means (±SD) or medians (Q1 - Q3), as appropriate, and categorical variables were determined as frequencies and proportions. We used the t-Student test (or Mann-Whitney) to compare continuous data and χ2 tests to compare categorical variables.

Construction of wGRS

For constructing an additive wGRS, 33 SNPs (Table S1) were surveyed for association with MACE in a Cox proportional hazard model. Those SNPs with a Hazard Ratio (HR)>1 were selected for the additive GRS. Subsequently, we counted the number of risk alleles for each of these SNPs, and the genotypes were coded as “0”, “1” and “2” for wild homozygous, heterozygous, and mutated homozygous, respectively. The additive weighted GRS (wGRS) was achieved by summing the product between the HR for each SNP and the number of risk alleles (0, 1, 2).

WGRS discriminative capacity to predict MACE

To estimate the wGRS discriminative capacity in MACE prediction, two analysis were performed: firstly, using TRFs as the baseline model, wGRS and clinical risk factors were sequentially added and compared; secondly, using TRFs + clinical risk factors as the baseline, wGRS was included and then compared. Harrell’s C-statistical approach tested the area under the Receiving Operating curve (ROC) of the models with and without wGRS and its statistical significance. C-statistic refers to the probability that predicting the outcome is better than chance comparing Cox regression models. Calibration was verified by Hosmer and Lemeshow goodness-of-fit test.

MACE reclassification

Net Reclassification Improvement (NRI) was calculated according to the continuous method. The number of individuals reclassified into higher and lower risk was applied to the two models with and without wGRS. NRI was designated as the percentage of subjects whose risk is changed (upwards or downwards) when adding the new marker (wGRS). Integrated Discrimination Improvement (IDI) can be defined as an increment of the difference between the means of predicted probabilities of two models: with and without the added marker (wGRS) (Steyerberg et al., 2010; Pencina et al., 2012).

Cumulative hazard rates according to wGRS

Event-free survival time was defined as the interval between the admission date to the study and the first event of interest. Patients who had not experienced MACE by the time of the last follow-up were censored. Unadjusted survival and its cumulative hazard curves for each of the outcomes were created by Kaplan-Meier estimator. Breslow test was performed to evaluate the differences between the high (higher than the median) and low (lower than the median) risk MACE groups.

The statistics methods used were those of the Statistical Package for the Social Sciences software version 25.0 (IBM, Armonk, NY, USA), MedCalc version and R (version 3.2.0). All P-values were two-sided, statistically significant for p<0.05.

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