{"doi":"10.1101/2022.09.02.506419","title":"Transcriptome and chromatin accessibility landscapes across 25 distinct human brain regions expand the susceptibility gene set for neuropsychiatric disorders","abstract":"Abstract Brain region- and cell-specific transcriptomic and epigenomic molecular 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 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 are strongly enriched for neuropsychiatric disease risk variants. Using an integrative approach, we characterized the function of the brain region-specific chromatin co-accessibility and gene-coexpression modules that are robustly associated with genetic risk for neuropsychiatric disorders. In addition, we identified a novel set of genes that is enriched for disease risk variants but is independent of cell-type specific gene expression and known susceptibility pathways. Our results provide a valuable resource for studying molecular regulation across multiple regions of the human brain and suggest a unique contribution of epigenetic modifications from subcortical areas to neuropsychiatric disorders.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299455,"datarank":0.2613436823674888,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.01992799550237369,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.01992799550237369,"corpus_percentile":41.12323044789974,"corpus_rank":7612,"citation_count":4,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8978,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":284407,"name":"Jaroslav Bendl","orcid":"0000-0001-9989-2720","position":1,"is_corresponding":false},{"id":807356,"name":"Ruth Misir","orcid":null,"position":2,"is_corresponding":false},{"id":21481,"name":"Zhiping Shao","orcid":"0009-0006-4889-6637","position":3,"is_corresponding":false},{"id":989830,"name":"Jonathan Edelstien","orcid":null,"position":4,"is_corresponding":false},{"id":29364,"name":"David A. Davis","orcid":"0000-0002-9323-6180","position":5,"is_corresponding":false},{"id":1201,"name":"Vahram Haroutunian","orcid":"0000-0001-5860-2512","position":6,"is_corresponding":false},{"id":437430,"name":"William K. Scott","orcid":"0000-0001-9336-6404","position":7,"is_corresponding":false},{"id":989831,"name":"Susanne Acker","orcid":null,"position":8,"is_corresponding":false},{"id":989286,"name":"Nathan Lawless","orcid":"0000-0002-3120-1126","position":9,"is_corresponding":false},{"id":1202,"name":"Gabriel E. Hoffman","orcid":"0000-0002-0957-0224","position":10,"is_corresponding":false},{"id":284413,"name":"John F. Fullard","orcid":"0000-0001-9874-2907","position":11,"is_corresponding":false},{"id":1203,"name":"Panos Roussos","orcid":"0000-0002-4640-6239","position":12,"is_corresponding":false},{"id":806414,"name":"Pengfei Dong","orcid":"0000-0003-3735-5158","position":0,"is_corresponding":true}],"reference_count":103,"raw_metadata":null,"created_at":"2026-07-19T00:31:44.904250Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}