A single-nuclei multiomics resource across four brain regions prioritises human neural cell types influencing brain-related traits
Year: 2026
Type: preprint
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.
Institution: University of Exeter
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Wellcome Trust, Alzheimer's Society, Alzheimer Society, National Institute for Health and Care Research, Department of Health and Social Care, European Commission, National Institutes of Health, HORIZON EUROPE Framework Programme, Medical Research Council, NIHR Oxford Biomedical Research Centre, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Gene Environment interactions in Mental health trajectories of Youth, Accelerating genetic research in Exeter with the Illumina NovaSeq 6000 DNA Sequencing System, G2703413578, Accelerating genetic research in Exeter with the Illumina NovaSeq 6000 DNA Sequencing System, Director of Functional Genomics Initiative, Partitioning the effects of schizophrenia risk variants on dynamics of the local synaptic translatome in cortex, G5522085319, G7762657818, Accelerated discovery of functional non-coding genomic variation using single molecule real-time (SMRT) sequencing., The next iteration of the AMP-T2D Knowledge Portal
OpenAlex ID: W7214297364