In contrast to our results and those of Janssens et al [3], Clayton [24] provided an expression for ROC under a polygenic model which is independent of population disease prevalence. His derivation assumes that the effect of each locus is additive on the log risk scale [25]. Slatkin [26] and we [27] have found that this model allows probabilities of disease that exceed one, which although they occur with low frequency can have substantial impact on the estimates of recurrence risk and genetic variance. Under this model there is a relationship between recurrence risk to monozygotic twins and to siblings of λMZ/ = 1; this ratio is not achieved when probabilities of disease are constrained to their natural parameter space of a maximum of 1. Furthermore, empirical estimates of the ratio of λMZ/ from the studies listed in Table 1 that provide estimates of λMZ and λS are mostly less than 1.0 [27], particularly for low prevalence diseases. Recognising that these estimates are subject to sampling variance, the estimates of λMZ/ are 1.1 (AMD), 0.4 (coronary artery disease), 0.8 (breast
