However, the overlap between DEG and gene association statistics was nominal (beta=0–0.04), and ASD- and BD-associated genes were neither differentially regulated in psychiatric disorders nor enriched for any disease-associated co-expression modules (Extended Data Fig. 6). This can be due to multiple reasons. First, ASD and BD GWAS have relatively limited power compared to SCZ and MDD, hence a more comprehensive picture may arise once we obtain better powered GWAS. Second, transcriptomic signatures do not necessarily reflect early events in the disease process that are directly impacted by genetic risk factors, but result from complex gene-environment interactions throughout the disease progression. Third, given that brain disorder-associated genes show cell-type specific enrichment (Fig. 3, Extended Data Fig. 4), they may affect gene regulation in a specific cell type(s) that may be missed by the bulk expression datasets. To test the third hypothesis, we compared gene association statistics with cell-type specific molecular signatures in AD pathology24. We found that AD-associated genes were significantly enriched for DEGs in microglia and oligodendrocytes, but not in neurons (Fig. 4a). While we cannot completely rule out the
