Cell type specific genetic effects on post transcriptional modifications

Nil Aygün led a study on identifying genetic variants affecting RNA editing and alternative polyadenylation sites in human neural progenitors and their differentiated neuronal progeny. More RNA-editing and isoforms utilizing longer polyadenylation sequences were observed in neurons, likely due to higher expression of genes encoding the proteins mediating these post-transcriptional events. We also detected hundreds of cell-type-specific editing quantitative trait loci (edQTLs) and alternative polyadenylation QTLs (apaQTLs). We found colocalizations of a neuron edQTL in CCDC88A with educational attainment and a progenitor apaQTL in EP300 with schizophrenia, suggesting genetically mediated post-transcriptional regulation during brain development lead to differences in brain function. The study can be found here.