The effect of disease prevalence (shown on the vertical axis) is not linearly related to sample size. In order to find genes with a smaller sample size, we need to collect a sample that has a lower prevalence. That could be achieved in one of two ways. If MD is truly a quantitative phenotype, then the extremes of the distribution will represent a less prevalent form of disease. We could take disease that is so severe that it has a prevalence of 0.5% or lower, so that fewer than 20,000 cases would provide 80% power to detect at least one locus. The problem is finding the appropriate severity scale.
