Figure 1.

Contour plot of minimum number of cases needed to maintain constant asymptotic power of 95% at a 5% significance level in the presence of phenotype misclassification for Alzheimer's disease ApoE example. We compute the increase in minimum cases () needed to maintain constant 95% asymptotic power at the 5% significance level (using a central χ² distribution with 5 degrees of freedom) in the presence of errors. Sample sizes are computed using equation (3). The affected and unaffected genotype frequencies are taken from a previous publication [9, 14]. In that work, the marker locus considered was ApoE and the disease phenotype was Alzheimer's disease. We use the LRT_ae estimates from table 5 of that work [9]. Six genotypes are observed in most populations. The frequencies we use to perform the sample size calculations in figure 1 are presented in the Methods section (Minimum sample size requirements in presence of phenotype misclassification – Alzheimer's Disease ApoE example). We assume that equal numbers of cases and controls are collected. Also, we specify a prevalence K = 0.02, which is consistent with recent published reports for Alzheimer's Disease in the U. S. [32]. Sample sizes are calculated for each misclassification parameter θ, φ ranging from 0.0 to 0.15 in increments of 0.01. The number of cases ranges from 484 when θ = φ = 0 to 10,187 when θ = φ = 0.15. In this figure, each (approximately) horizontal line represents a constant sample size as a function of the misclassification parameters θ and φ. For two consecutive horizontal lines, the values in between those lines (represented by different colors) have sample sizes that are between the sample sizes indicated by the two horizontal lines.