p -value histogram for (a) schizophrenia/control and (b) bipolar/control (expression data, all subjects). p-values of truly null features are distributed uniformly, while p-values of significant features are clustered around 0.0. This translates to a flat histogram with a peak at 0.0, as in (b). The p-values in (a) are biased towards 1.0 causing the q-value estimates to be conservative. The reason for observing such biased distributions is currently not very well understood .