Wray and Visscher asked this question about the genetic architecture of schizophrenia (Wray and Visscher, 2010). Their answer involved finding a phenotype with a genetic architecture predicted to be similar to schizophrenia and for which many genetic loci have been found. They suggested, from similar heritability estimates, risks to relatives, and the disease prevalence, that the genetic architecture of schizophrenia resembles that of height. In order to compare genetic analysis of height with schizophrenia, they assume that genetic liability to schizophrenia is quantitative and that the dichotomous nature of schizophrenia arises because the number of predisposing alleles in some individuals exceeds a certain threshold. For example, an individual with predisposing alleles at 100 loci or more might present with schizophrenia, while someone with fewer such alleles would show no symptoms. By considering that disease prevalence represents the fraction of individuals whose genetic susceptibility exceeds this threshold, and that schizophrenia has otherwise the same genetic architecture as height, it is possible to apply what we know from height GWAS data to estimate sample sizes needed to detect schizophrenia risk loci (Yang et al., 2010b).
