Figure 1. Phenotypes under the gene-based model.

(a) Phenotype depends only on the number of causative mutations present on each haplotype, and not on whether an individual is homo- or heterozygous for particular mutations. Thus, the two diploids shown are equivalent in their expected phenotype, as both diploids contain one haplotype with two causative mutations, and a second haplotype with three such mutations. (b) Phenotype is calculated as the geometric mean of the effects of each haplotype, and is therefore determined primarily by the haplotype closest to wild-type. The panel shows the expected phenotype for diploids with different combinations of mutations on each haplotype, assuming a constant effect size of 0.05 per mutation. (c) Quantile-quantile plots of phenotypes resulting from the simulation. The x-axis is the quantiles of a unit Gaussian, and the y-axis is the z-score normalized quantiles observed in a simulated population. For three different parameter values, the phenotypes of 20,000 diploids from a single simulated population are shown. At moderate average effect sizes (λ) (0.10 in the panel), there tends to be an excess of individuals with modestly-large phenotypes, whereas with large λ, a population typically contains proportionally more individuals with large phenotypic values. (d). Broad-sense heritability as a function of λ, the mean effect size of a causative disease mutation. Plotted are the mean values ±1 standard deviation, calculated from the simulation output.