We identified significant differences in the location and gene targets of regionally heterogeneous and pan-regional cis-eQTL signals. We found that, while the distribution of regionally heterogeneous and pan-regional cis-eQTLs were both centered around the transcription start site, regionally heterogeneous cis-eQTLs were more dispersed, and this change in distribution was statistically significant (two-sample Kolmogorov-Smirnov test P = 1.6 × 10−9). Notably, we also found that the gene targets of regionally heterogeneous cis-eQTL signals systematically differed from the gene targets of pan-regional cis-eQTL signals in biologically relevant ways. Using gene ontology enrichment analysis, genes regulated by regionally heterogeneous cis-eQTL signals were significantly enriched for terms related to synaptic transmission (GO:0007268, synaptic transmission; Bonferroni-corrected modified Fisher’s exact P = 0.018), while genes regulated by pan-regional cis-eQTL signals were related to more basic cellular functions, including Golgi apparatus and organelle lumen (GO:0005794, Golgi apparatus; Bonferroni-corrected modified Fisher’s exact P = 0.00130; GO:0070013, intracellular organelle lumen; Bonferroni-corrected modified Fisher’s exact P = 0.0182). These findings suggest that regionally heterogeneous control of gene regulation is predominantly directed at genes involved in specialized cellular functions, as within the human brain the most specialized of functions would be predicted to be synaptic transmission.
