An alternative approach would be to undertake a joint analysis of the original 13 annotations from the multiple-tissue analysis. However, joint analysis of 13 highly correlated annotations is likely to be underpowered, while re-computing t-statistics within the brain allows us to construct new annotations with lower correlations (Figure S7), increasing our power. Moreover, differential expression within the brain may allow us to isolate signals from cell types or processes that are unique to a single brain region, separately from the cell types or processes that are unique to the brain but shared among brain regions. Thus, we use differential expression within the brain, rather than joint analysis of the original annotations, to differentiate among brain regions.