the inheritance pattern, if any, is currently unclear [31]). Such variants, although genetic, do not contribute to the similarity between relatives, and so would be included in the environmental component when partitioning variance. Under these circumstances it is possible that a genomic profile could exceed the AUCmax based on sibling recurrence ratio. Our calculations assume that we know the population parameters K and λS (and therefore ). Estimates of these parameters are sometimes based on small sample size and are subject to sampling bias or different definitions of the disease. In particular, prevalence rates can depend on the age distribution of the population in which they are measured. In addition, recurrence risk ratios of relatives have a maximum possible value which is dependent on the disease prevalence, so that higher risk ratios are achievable when disease prevalence is lower; and estimates of sibling risk ratio and disease prevalence calculated in different studies sometimes reflect this dependence. In Table 1, we included two different estimates for both schizophrenia and bipolar disorder, but for these examples the estimates of AUCmax are robust to the magnitude of differences reported in genetic epidemiology parameters for individual diseases. At present, genomic profiles based on validated
