{"doi":"10.1101/2022.04.01.486135","title":"Spatial, transcriptomic and epigenomic analyses link dorsal horn neurons to chronic pain genetic predisposition","abstract":"Key mechanisms underlying chronic pain occur within the neural circuitry of the dorsal horn. Recent genome-wide association studies (GWAS) have identified genetic variants associated with the predisposition to chronic pain. However, most of these variants lie in regulatory non-coding regions that have so far not been linked to spinal cord function. Here, we take a multi-species approach to determine whether chronic pain variants impact regulatory elements of dorsal horn neurons. We first built a more comprehensive single cell atlas; filling gaps by generating a high-quality Rhesus macaque atlas and integrating it with human and mouse. With cellular-resolution spatial transcriptomics, we mapped the laminar distributions of the resulting species-conserved neuron subtypes, uncovering an unexpected organization. Lastly, we generated a mouse single-nucleus open chromatin atlas to partition the heritability of chronic pain traits. From this, we identified strong, selective associations between specific, conserved neuron subtypes and major forms of chronic pain.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298618,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"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":336248,"name":"Michael J. Leone","orcid":"0000-0002-0218-8612","position":1,"is_corresponding":false},{"id":367579,"name":"Michael Kleyman","orcid":"0000-0001-9994-2652","position":2,"is_corresponding":false},{"id":570873,"name":"Alexander Chamessian","orcid":"0000-0002-7775-2062","position":3,"is_corresponding":false},{"id":78772,"name":"BaDoi N. Phan","orcid":"0000-0001-6331-5980","position":4,"is_corresponding":false},{"id":987633,"name":"Bettega Costa Lopes","orcid":"0000-0002-8090-0273","position":5,"is_corresponding":false},{"id":987985,"name":"Vijay Kiran Cherupally","orcid":null,"position":6,"is_corresponding":false},{"id":247855,"name":"Myung‐chul Noh","orcid":"0009-0009-9735-1942","position":7,"is_corresponding":false},{"id":248911,"name":"Kelly A. Corrigan","orcid":null,"position":8,"is_corresponding":false},{"id":782825,"name":"Deepika Yeramosu","orcid":"0000-0003-3963-8995","position":9,"is_corresponding":false},{"id":987986,"name":"Michael E Franusich","orcid":null,"position":10,"is_corresponding":false},{"id":987987,"name":"Riya Podder","orcid":null,"position":11,"is_corresponding":false},{"id":987988,"name":"Sumitra Lele","orcid":null,"position":12,"is_corresponding":false},{"id":279173,"name":"Stephanie Shiers","orcid":"0000-0002-9646-1850","position":13,"is_corresponding":false},{"id":368278,"name":"Byungsoo Kang","orcid":null,"position":14,"is_corresponding":false},{"id":561985,"name":"Meaghan M. Kennedy Ng","orcid":"0000-0003-4612-7560","position":15,"is_corresponding":false},{"id":987989,"name":"Viola Chen","orcid":null,"position":16,"is_corresponding":false},{"id":78767,"name":"Ziheng Chen","orcid":"0000-0001-5709-8529","position":17,"is_corresponding":false},{"id":635380,"name":"Richard P. Dum","orcid":null,"position":18,"is_corresponding":false},{"id":6269,"name":"David A. Lewis","orcid":"0000-0002-3225-6778","position":19,"is_corresponding":false},{"id":249986,"name":"Yawar J. Qadri","orcid":"0000-0003-2138-4018","position":20,"is_corresponding":false},{"id":257966,"name":"Theodore J. Price","orcid":"0000-0002-6971-6221","position":21,"is_corresponding":false},{"id":16451,"name":"Andreas R. Pfenning","orcid":"0000-0002-3447-9801","position":22,"is_corresponding":false},{"id":247861,"name":"Rebecca P. Seal","orcid":"0000-0003-4955-703X","position":23,"is_corresponding":false},{"id":247853,"name":"Cynthia M. 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