random (with replacement) from the remaining 999 permutations. This process was repeated 1000 times. The empirical test of the number of significant genes being higher than expected under the null hypothesis of no association was carried out by comparing the observed number of significant genes to the empirical distribution. The calculated level of significance was based upon the distributions of the number of significant genes under the null hypothesis which formally passed the test for normality (in all instances both the skewness and kurtosis coefficients were between - 0.5 and 0.5).
