Table 1.
A 2×2 classification table.
Figure 1.
Predictiveness curves for different levels of variance explained.
The percentile of measurable liability is equivalent to the percentile of absolute risk. The disease probability in the population is set at 0.1.
Figure 2.
Area under the predictiveness curve and proportion of cases explained.
The proportion of cases explained by the 20% population at the highest risk is equal to the green shaded area divided by the total area under the predictiveness curve.
Table 2.
A typical re-classification table with 3 risk categories.
Table 3.
Predictive indices under different combinations of overall disease probability (K) and variance explained ().
Figure 3.
Comparison of the predictiveness curves from simulated data and theoretical calculations.
The predictiveness curve plots the predicted risk against risk precentiles. The overall disease risk K = 0.005 and 30 loci from Table S1 were included. The black dotted line represents results from simulations and the green solid line is obtained by theoretical calculations. The total variance explained is equal to 0.0442. The theoretical estimates of predicted risks are from equation (1), i.e. , where T is the liability threshold,
is the variance explained and p is the percentile of measurable risk derived from known genetic factors.
Figure 4.
Comparison of predicted risk distributions from simulated data and theoretical calculations.
The overall disease risk K = 0.005 and 30 loci from Table S1 were included. The histogram was obtained from simulations data, while the blue line showing probability density was derived from theoretical calculations. The theoretical distribution was obtained by differentiating the cumulative density function of estimated risks.
Table 4.
Improvement in predictive indices with increase in variance explained.
Table 5.
Predictive indices for nine complex diseases.
Figure 5.
Graphs showing risk distribution and predictive power of known susceptibility variants for breast cancer.
A: ROC curve ; B: predictiveness curve (predicted risk against risk perecentile) ; C: Cumulative density function of predicted risks ; D: Probability density function of predicted risks ; E: Probability density function of predicted risks in the population (blue solid line) and in cases (green dotted line) ; F: Proportion of cases explained against proportion of population at highest risk. While the plots A and F appear similar, they are not identical as shown mathematically in the text. Similar graphs for other diseases are presented in Figures S1, S2, S3, S4, S5, S6, S7, S8.