We next performed a sQTL study to identify local genetic effects that drive variation in RNA splicing in the DLFPC. First, we assessed the splice events from the LeafCutter20 algorithm (Fig. 1); 30% of these 53,251 intron excision clusters are novel splicing events, not previously reported in other sQTL studies. The PSI values were adjusted for known and hidden factors (15 principal components) and then fit to imputed SNP data using an additive linear model implemented in fastQTL26 (Online Methods; Supplementary Fig. 5). At FDR < 0.05, we found 9,028 sQTLs in 3,006 genes (Supplementary Table 10). As expected, splicing was most strongly affected by variants in the splice region itself (59.8%): 20.2% of variants are mapped to splice acceptor sites and 16.4% to splice donor sites. The remaining (23.2%) mapped to other splice regions or are found within an intron (Supplementary Fig. 6). Further, sQTLs are mapped to distinct regulatory features as defined by 15 chromatin states in DLPFC27: sQTLs were significantly enriched in actively transcribed regions and enhancers. They are depleted in repressed chromatin marked with polycomb, heterochromatin, and quiescent regions (Fig. 3a), consistent with the diminished transcription noted in these regions.
