In theory drug treatment could have a strong effect on the abundance of specific transcripts in cases with SCZ and thereby induce a subset of genes to cluster together and have different co-expression patterns compared to controls. To explore this hypothesis, we performed enrichment analysis of drug gene expression signatures (see “Drug effects on differential expression” section), and identified an overlap for 3 out of 18 drug signature datasets with M2c. While the overlap was significant after correcting for multiple testing, this is not surprising because M2c contains multiple receptor subunits and genes underlying synaptic neurotransmission, including direct targets of different neuroleptics. We then explored the hypothesis that genes affected by medications (or belonging to a drug signature) are differentially expressed between cases with SCZ and controls, which subsequently leads to loss of density in SCZ modules. To explore this hypothesis, we focused on genes that cluster within the M2c module and examined whether the distribution of the differentially expressed genes significance (estimated as −log10 P value) is different for genes with (“Drug”) and without (“NonDrug”) a drug signature. We
