Table 1.
OR | Frequency | Variants (n) | AUC | IDI | NRI(>0.01) | NRI categorical | ||||
---|---|---|---|---|---|---|---|---|---|---|
Genetic | Combined | Δ | Total | Cases | Controls | |||||
Rare variants | ||||||||||
2 | 0.0001 | 1 | 0.50 | 0.76 | 0 | 0 | 0 | 0 | 0 | 0 |
0.001 | 1 | 0.50 | 0.76 | 0 | 0 | 0 | 0 | 0 | 0 | |
0.005 | 1 | 0.50 | 0.76 | 0 | 0 | -0.01 | 0 | 0 | 0 | |
0.01 | 1 | 0.51 | 0.76 | 0 | 0 | -0.03 | 0 | 0 | 0 | |
5 | 0.0001 | 1 | 0.50 | 0.76 | 0 | 0 | 0 | 0 | 0 | 0 |
0.001 | 1 | 0.50 | 0.76 | 0 | 0 | -0.01 | 0 | 0 | 0 | |
0.005 | 1 | 0.51 | 0.76 | 0 | 0 | -0.05 | 0.01 | 0.01 | 0 | |
0.01 | 1 | 0.52 | 0.77 | 0.01 | 0.01 | -0.10 | 0.02 | -0.01 | 0.03 | |
10 | 0.0001 | 1 | 0.50 | 0.76 | 0 | 0 | 0 | 0 | 0 | 0 |
0.001 | 1 | 0.50 | 0.76 | 0 | 0 | -0.03 | 0.00 | 0 | 0.01 | |
0.005 | 1 | 0.52 | 0.77 | 0.01 | 0.02 | -0.11 | 0.02 | -0.01 | 0.03 | |
0.01 | 1 | 0.54 | 0.78 | 0.02 | 0.03 | -0.13 | 0.04 | -0.02 | 0.06 | |
Common variants | ||||||||||
1.14-1.45a | 0.03-0.84* | 10 | 0.59 | 0.77 | 0.01 | 0.01 | 0.20 | 0.04 | 0.01 | 0.04 |
aUsing parameters from the top 10 (that is, in terms of P value) uncorrelated SNPs in the CHARGE AF meta-analysis; in the table are listed the range of OR and allele frequency [22]. Variables included in the clinical risk score were: age, weight, height, systolic blood pressure (SBP), diastolic blood pressure (DBP), diabetes, medication for hypertension, history of congestive heart failure, history of myocardial infarction, smoking status, and race. Disease risk is 4% and population size is 200,000 for rare variants scenarios and 20,000 for common variants scenarios. Results are median values from 200 simulations.
AUC, area under the receiver operating characteristic curve; ΔAUC, change in AUC between the model with and without genetic variants; IDI, integrated discrimination improvement; NRI, net reclassification improvement (cutoffs 2.5% and 5%); OR, odds ratio.