To calculate empirical gene-wide significance for each gene, we performed 1000 genome-wide permutations for each GWAS data set. For each gene in each permutation we obtained the smallest p and the product of p values as for the original dataset. We then calculated the three empirical p-values for each gene in the observed data by determining the proportion of permuted datasets where the corresponding p-value obtained for each gene was equal to or smaller than was observed in the true dataset.
