High Penetrance (β1 = 2)
                        β2 = 0.7                       β2 = 1.6
Model Bias% SE RMSE Bias% SE RMSE
Independent -33.80 0.080 0.348 -54.75 0.082 0.553
Frailty -4.99 0.097 0.136 -23.41 0.100 0.259
2-gene model -7.90 0.115 0.170 -14.22 0.110 0.198
                                                       Low Penetrance (β1 = 1)
                        β2 = 0.7                       β2 = 1.6
Model Bias% SE RMSE Bias% SE RMSE
Independent -12.82 0.076 0.156 -24.36 0.070 0.254
Frailty -2.36 0.085 0.116 -13.48 0.078 0.163
2-gene model 0.44 0.099 0.133 -2.11 0.092 0.126
Bias% = Bias×100
Table 3: (Second gene variation) Estimating the log hazards ratio of major gene effect in the presence of a second gene: Bias, robust standard error (SE) and root mean square error (RMSE) in comparison of the three models.