MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size

Lafferty, M. J.; Aygün, N.; Krupa, O.; Liang, D.; Wolter, J. M.; Geschwind, D. H.; de la Torre-Ubieta, L.; Stein, J. L.

doi:10.1101/2022.03.31.486585

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bioRxiv · 10.1101/2022.03.31.486585

MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size

Lafferty, M. J.·Aygün, N.·Krupa, O.·Liang, D.·Wolter, J. M.·Geschwind, D. H.·de la Torre-Ubieta, L.·Stein, J. L.

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Abstract

Expression quantitative trait loci (eQTL) data have proven important for linking non-coding loci to protein-coding genes. But eQTL studies rarely measure microRNAs (miRNAs), small non-coding RNAs known to play a role in human brain development and neurogenesis. Here, we performed small-RNA sequencing across 212 mid-gestation human neocortical tissue samples, measured 907 expressed miRNAs, discovering 111 of which were novel, and identified 85 local-miRNA-eQTLs. Colocalization of miRNA-eQTLs with GWAS summary statistics yielded one robust colocalization of miR-4707-3p expression with educational attainment and brain size phenotypes, where the miRNA expression increasing allele was associated with decreased brain size. Exogenous expression of miR-4707-3p in primary human neural progenitor cells decreased expression of predicted targets and increased cell proliferation, indicating miR-4707-3p modulates progenitor gene regulation and cell fate decisions. Integrating miRNA-eQTLs with existing GWAS yielded evidence of a miRNA that may influence human brain size and function via modulation of neocortical brain development.

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Lafferty, M. J., Aygün, N., Krupa, O., Liang, D., Wolter, J. M., Geschwind, D. H., de la Torre-Ubieta, L., Stein, J. L.. 2022-04-01. MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size. https://doi.org/10.1101/2022.03.31.486585

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