We matched in vitro medication signatures with TUD signatures from brain tissue transcriptome-wide association analyses (conducted using S-PrediXcan). This consisted of Amygdala, Anterior Cingulate Cortex BA24, Caudate Basal Ganglia, Cerebellar Hemisphere, Cerebellum, Cortex, Frontal Cortex BA9, Hippocampus, Hypothalamus, Nucleus Accumbens Basal Ganglia, Putamen Basal Ganglia, Substantia Nigra, and Pituitary brain regions. We computed weighted Pearson correlations between transcriptome-wide brain associations and in vitro L1000 compound signatures,36 weighting each gene by its proportion of heritability explained, using the metafor package (version 3.8–1) in R. We treated each L1000 compound as a fixed effect incorporating the effect size (rweighted) and sampling variability (se2r_weighted) from all signatures of a compound (e.g., across all time points, cell lines, doses). Brain region was included as a random effect to account for any tissue specific heterogeneity. Both the genes for the transcriptome wide association analysis input and the medications from our drug repurposing analyses were required to survive a Bonferroni correction for multiple testing (transcriptome-wide correction=0.05/14,199=3.52E-06; Perturbagen correction =0.05/3,897=1.28E-05).
