A multi-regional human brain atlas of chromatin accessibility and gene expression facilitates promoter-isoform resolution genetic fine-mapping
Abstract Brain region- and cell-specific transcriptomic and epigenomic features are associated with heritability for neuropsychiatric traits, but a systematic view, considering cortical and subcortical regions, is lacking. Here, we provide an atlas of chromatin accessibility and gene expression prof...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54448-y |
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| Summary: | Abstract Brain region- and cell-specific transcriptomic and epigenomic features are associated with heritability for neuropsychiatric traits, but a systematic view, considering cortical and subcortical regions, is lacking. Here, we provide an atlas of chromatin accessibility and gene expression profiles in neuronal and non-neuronal nuclei across 25 distinct human cortical and subcortical brain regions from 6 neurotypical controls. We identified extensive gene expression and chromatin accessibility differences across brain regions, including variation in alternative promoter-isoform usage and enhancer-promoter interactions. Genes with distinct promoter-isoform usage across brain regions were strongly enriched for neuropsychiatric disease risk variants. Moreover, we built enhancer-promoter interactions at promoter-isoform resolution across different brain regions and highlighted the contribution of brain region-specific and promoter-isoform-specific regulation to neuropsychiatric disorders. Including promoter-isoform resolution uncovers additional distal elements implicated in the heritability of diseases, thereby increasing the power to fine-map risk genes. Our results provide a valuable resource for studying molecular regulation across multiple regions of the human brain and underscore the importance of considering isoform information in gene regulation. |
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| ISSN: | 2041-1723 |