This model was modified to test sex differences in the liability to a condition by applying separate thresholds for males and females by Carter, 66 depicted in Figure 2 by light gray for males and dark gray for females. 66 To test whether there is a sex difference in the transmission of a disorder, it is expected that the less frequently affected sex will have a higher threshold of liability for the disorder (ie, they require a greater number of genetic and/or environmental risk factors before manifesting the disorder than the more frequently affected sex). This implies that there is greater loading of risk factors among relatives of the less commonly affected sex, so their relatives would be more likely to manifest the disorder. This expectation can be tested systematically in family and twin studies through analysis of sex of proband effects as described below. 61
