Extended Data Fig. 2: Simulations of recessive and additive effects at different MAFs.

Here, we generated genotype counts of wild types, heterozygotes and mutant homozygotes in 200,000 individuals of a variant with an allele frequency of 0.01 following Hardy Weinberg Equilibrium (R library: HardyWeinberg) and random controls and cases of a disease with a prevalence of 0.05 (see also Supplementary Note 2). In a we simulate a recessive association. Here, we set the probability of homozygotes to develop the disease to 5x compared to wild type and the heterozygous effect to 1 (= no effect). In this histogram we show on the x-axis, the log10 p-value of the recessive model - the log10 p-value of the additive model (method: logistic regression). In b we simulate an additive association. Here, we set the homozygous effect to 1.5x and the heterozygous effect to 2.25. In this histogram we show on the x-axis, the log10 p-value of the additive model - the log10 p-value of the recessive model (method: logistic regression).