A single-cell eQTL atlas of the developing human brain

Genetic influences on gene expression in the developing brain are likely to impact a variety of human traits, including susceptibility to neuropsychiatric disorders. However, to date, expression quantitative trait loci (eQTL) studies of the prenatal human brain have been based on ‘bulk’ tissue, where gene expression measures are averaged across all constituent cell types. Here, we performed single nuclei RNA sequencing (snRNA-Seq) and genome-wide genotyping on cerebral cortex from 134 unrelated samples from the second trimester of gestation to provide the first single nuclei eQTL atlas of the prenatal human brain. We identify 3121 unique eGenes across 7 major cell types and 12 of their subtypes, combining these data with large-scale genome-wide association study (GWAS) data for neuropsychiatric disorders to implicate particular cell populations of the developing human brain in the etiology of these conditions and to identify specific gene expression differences within them that credibly confer susceptibility. Our study significantly advances knowledge of the cellular origins of neuropsychiatric disorders and provides a resource for interpreting GWAS findings for other conditions with a potential neurodevelopmental component.