Abstract
AbstractExpression 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.
Publisher
Cold Spring Harbor Laboratory
Reference107 articles.
1. Grasby KL , Jahanshad N , Painter JN , Colodro-Conde L , Bralten J , Hibar DP , et al. The genetic architecture of the human cerebral cortex. Science. 2020 Mar 20;367(6484).
2. Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals
3. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
4. Knol MJ , Poot RA , Evans TE , Satizabal CL , Mishra A , van der Auwera S , et al. Genetic variants for head size share genes and pathways with cancer. BioRxiv. 2020 Jul 16;
5. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses