probably schizophrenia [13]. Different genetic models may underlie genetic heterogeneity. One possibility is that multiple different variants located across the genome have independent influence on disease risk, such that each variant explains only a small fraction of all affected individuals. Another scenario is that the function of each haplotype of a gene is destroyed if one (or more) lethal mutations occur on the haplotype. In this manner, an individual must have at least one mutation on each of the two haplotypes to be predisposed for the disease (see the Recessive-Set model in Figure 1). In both of these models, the marginal PAR of each mutation may be very low, even when the disease is highly heritable.
