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bioRxiv · 10.1101/2023.08.30.555019

Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis

Aygün, N.·Krupa, O.·Mory, J.·Le, B.·Valone, J.·Liang, D.·Love, M. I.·Stein, J. L.
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Abstract

The function of some genetic variants associated with brain-relevant traits has been explained through colocalization with expression quantitative trait loci (eQTL) conducted in bulk post-mortem adult brain tissue. However, many brain-trait associated loci have unknown cellular or molecular function. These genetic variants may exert context-specific function on different molecular phenotypes including post-transcriptional changes. Here, we identified genetic regulation of RNA-editing and alternative polyadenylation (APA), within a cell-type-specific population of human neural progenitors and neurons. 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.

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Aygün, N., Krupa, O., Mory, J., Le, B., Valone, J., Liang, D., Love, M. I., Stein, J. L.. 2023-09-01. Genetics of cell-type-specific post-transcriptional gene regulation during human neurogenesis. https://doi.org/10.1101/2023.08.30.555019

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