To match inferred transcriptional patterns of PAU with transcriptional patterns induced by perturbagens, we related our S-PrediXcan results to signatures from the Library of Integrated Network-based Cellular Signatures L1000 database80. This database catalogs in vitro gene expression profiles (signatures) from thousands of compounds from >80 human cell lines (level 5 data from phase I: GSE92742 and phase II: GSE70138). Our analyses included signatures of 829 chemical compounds in five neuronal cell lines (NEU, NPC, MNEU.E, NPC.CAS9 and NPC.TAK). To test significance of the association between PAU signatures and Library of Integrated Network-based Cellular Signatures perturbagen signatures, we followed the procedure from So et al.81. Briefly, we computed weighted (by proportion of heritability explained) Pearson correlations between transcriptome-wide brain associations and in vitro L1000 compound signatures using the metafor package82 in R. We treated each L1000 compound as a fixed effect incorporating the effect size (rweighted) and sampling variability (se2) from all signatures of a compound (for example, across all time points and doses). We only report those perturbagens that were associated after Bonferroni correction (P < 0.05/829 = 6.03 × 10−5).
