A single-nuclei multiomics resource across four brain regions prioritises human neural cell types influencing brain-related traits

Abstract

Genetic studies have identified thousands of variants associated with brain-related traits. However, the majority of these map to non-coding regions and their causal roles and functional consequences are unclear. In this study, we profiled gene expression and chromatin accessibility in ~140,000 individual nuclei from 40 post-mortem adult human brain samples from 11 donors spanning four brain regions (amygdala, hippocampus, hypothalamus and prefrontal cortex). Integrating these data with genome-wide association study statistics allowed us to prioritise specific neural cell populations relevant for complex traits. Concordant with epidemiological evidence, we prioritise similar neuronal cell populations for BMI, schizophrenia, bipolar disorder and age at menarche associated variants. Our paired multiomic data also provides support for putative enhancer-gene relationships relevant to Alzheimer's disease. These data provide a valuable resource to help interpret trait-associated genetic variation and nominate effector transcripts and cellular pathways relevant to brain-related phenotypes.