High Penetrance (β1 = 2)                              β2 = 0.7                           β2 = 1.6 Model Bias% SE RMSE Bias% SE RMSE Independent 7.14 0.014 0.073 9.14 0.010 0.092 Frailty -19.64 0.072 0.210 -8.70 0.045 0.101 2-gene model 1.90 0.073 0.086 3.64 0.036 0.057                                                                 Low Penetrance (β1 = 1)                              β2 = 0.7                           β2 = 1.6 Model Bias% SE RMSE Bias% SE RMSE Independent 17.13 0.025 0.173 18.86 0.020 0.190 Frailty -9.72 0.062 0.120 -1.37 0.047 0.065 2-gene model 13.21 0.109 0.186 12.12 0.073 0.147 Bias% = Bias×100

Table 4: (Second gene variation) Estimating the penetrance by age 70 among carriers in the presence of a second gene: Bias, robust standard error (SE) and root mean square error (RMSE) in comparison of the three models.