{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T12:09:09Z","timestamp":1775218149930,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"D1","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01LM012806"],"award-info":[{"award-number":["R01LM012806"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RP180734"],"award-info":[{"award-number":["RP180734"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Data Science and Informatics Core for Cancer Research","award":["RP170668"],"award-info":[{"award-number":["RP170668"]}]},{"name":"Data Science and Informatics Core for Cancer Research","award":["R03DE027711"],"award-info":[{"award-number":["R03DE027711"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>During the past decade, genome-wide association studies (GWAS) have identified many genetic variants with susceptibility to several thousands of complex diseases or traits. The genetic regulation of gene expression is highly tissue-specific and cell type-specific. Recently, single-cell technology has paved the way to dissect cellular heterogeneity in human tissues. Here, we present a reference database for GWAS trait-associated cell type-specificity, named Cell type-Specific Enrichment Analysis DataBase (CSEA-DB, available at https:\/\/bioinfo.uth.edu\/CSEADB\/). Specifically, we curated total of 5120 GWAS summary statistics data for a wide range of human traits and diseases followed by rigorous quality control. We further collected &amp;gt;900 000 cells from the leading consortia such as Human Cell Landscape, Human Cell Atlas, and extensive literature mining, including 752 tissue cell types from 71 adult and fetal tissues across 11 human organ systems. The tissues and cell types were annotated with Uberon and Cell Ontology. By applying our deTS algorithm, we conducted 10 250 480 times of trait-cell type associations, reporting a total of 598 (11.68%) GWAS traits with at least one significantly associated cell type. In summary, CSEA-DB could serve as a repository of association map for human complex traits and their underlying cell types, manually curated GWAS, and single-cell transcriptome resources.<\/jats:p>","DOI":"10.1093\/nar\/gkaa1064","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T19:12:51Z","timestamp":1603307571000},"page":"D862-D870","source":"Crossref","is-referenced-by-count":28,"title":["CSEA-DB: an omnibus for human complex trait and cell type associations"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1874-7893","authenticated-orcid":false,"given":"Yulin","family":"Dai","sequence":"first","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5549-3082","authenticated-orcid":false,"given":"Ruifeng","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}]},{"given":"Astrid Marilyn","family":"Manuel","sequence":"additional","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}]},{"given":"Andi","family":"Liu","sequence":"additional","affiliation":[{"name":"Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4523-4153","authenticated-orcid":false,"given":"Peilin","family":"Jia","sequence":"additional","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3477-0914","authenticated-orcid":false,"given":"Zhongming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"},{"name":"Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA"},{"name":"MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA"}]}],"member":"286","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"2021010313115022300_B1","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41588-018-0081-4","article-title":"Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types","volume":"50","author":"Finucane","year":"2018","journal-title":"Nat. Genet."},{"key":"2021010313115022300_B2","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nature24277","article-title":"Genetic effects on gene expression across human tissues","volume":"550","author":"GTEx Consortium; Laboratory, Data Analysis and Coordinating Center (LDACC)-Analysis Working Group; Statistical Methods groups-Analysis Working Group; Enhancing GTEx (eGTEx) groups; NIH Common Fund; NIH\/NCI; NIH\/NHGRI; NIH\/NIMH; NIH\/NIDA","year":"2017","journal-title":"Nature"},{"key":"2021010313115022300_B3","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1136\/jmedgenet-2019-106490","article-title":"Diverse types of genomic evidence converge on alcohol use disorder risk genes","volume":"57","author":"Dai","year":"2020","journal-title":"J. Med. Genet."},{"key":"2021010313115022300_B4","doi-asserted-by":"crossref","first-page":"318","DOI":"10.3389\/fgene.2019.00318","article-title":"A convergent study of genetic variants associated with crohn's disease: evidence from GWAS, gene expression, methylation, eQTL and TWAS","volume":"10","author":"Dai","year":"2019","journal-title":"Front. Genet."},{"key":"2021010313115022300_B5","doi-asserted-by":"crossref","first-page":"3842","DOI":"10.1093\/bioinformatics\/btz138","article-title":"deTS: tissue-specific enrichment analysis to decode tissue specificity","volume":"35","author":"Pei","year":"2019","journal-title":"Bioinformatics"},{"key":"2021010313115022300_B6","doi-asserted-by":"crossref","first-page":"D794","DOI":"10.1093\/nar\/gkx1081","article-title":"The encyclopedia of DNA elements (ENCODE): data portal update","volume":"46","author":"Davis","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"2021010313115022300_B7","first-page":"D1022","article-title":"TSEA-DB: a trait-tissue association map for human complex traits and diseases","volume":"48","author":"Jia","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2021010313115022300_B8","volume-title":"Introduction to the Human Body","author":"Tortora","year":"2017"},{"key":"2021010313115022300_B9","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/nbt.4038","article-title":"Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain","volume":"36","author":"Lake","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"2021010313115022300_B10","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.1038\/s41467-018-06318-7","article-title":"Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations","volume":"9","author":"MacParland","year":"2018","journal-title":"Nat. Commun."},{"key":"2021010313115022300_B11","doi-asserted-by":"crossref","first-page":"24100","DOI":"10.1073\/pnas.1914143116","article-title":"Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration","volume":"116","author":"Voigt","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021010313115022300_B12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-019-1906-x","article-title":"scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation","volume":"21","author":"Madissoon","year":"2019","journal-title":"Genome Biol."},{"key":"2021010313115022300_B13","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/s41591-019-0468-5","article-title":"A cellular census of human lungs identifies novel cell states in health and in asthma","volume":"25","author":"Vieira\u00a0Braga","year":"2019","journal-title":"Nat. Med."},{"key":"2021010313115022300_B14","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/s41586-020-2157-4","article-title":"Construction of a human cell landscape at single-cell level","volume":"581","author":"Han","year":"2020","journal-title":"Nature"},{"key":"2021010313115022300_B15","doi-asserted-by":"crossref","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2021010313115022300_B16","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/s41588-019-0404-0","article-title":"Abundant associations with gene expression complicate GWAS follow-up","volume":"51","author":"Liu","year":"2019","journal-title":"Nat. Genet."},{"key":"2021010313115022300_B17","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/ng.3570","article-title":"Detection and interpretation of shared genetic influences on 42 human traits","volume":"48","author":"Pickrell","year":"2016","journal-title":"Nat. Genet."},{"key":"2021010313115022300_B18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12864-018-5373-7","article-title":"Investigation of multi-trait associations using pathway-based analysis of GWAS summary statistics","volume":"20","author":"Pei","year":"2019","journal-title":"BMC Genomics"},{"key":"2021010313115022300_B19","doi-asserted-by":"crossref","first-page":"e1004219","DOI":"10.1371\/journal.pcbi.1004219","article-title":"MAGMA: generalized gene-set analysis of GWAS data","volume":"11","author":"de\u00a0Leeuw","year":"2015","journal-title":"PLoS Comput. Biol."},{"key":"2021010313115022300_B20","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.cmet.2016.08.020","article-title":"Single-cell transcriptome profiling of human pancreatic islets in health and type 2 diabetes","volume":"24","author":"Segerstolpe","year":"2016","journal-title":"Cell Metab."},{"key":"2021010313115022300_B21","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41586-018-0698-6","article-title":"Single-cell reconstruction of the early maternal-fetal interface in humans","volume":"563","author":"Vento-Tormo","year":"2018","journal-title":"Nature"},{"key":"2021010313115022300_B22","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.cell.2017.09.004","article-title":"Single-Cell analysis of human pancreas reveals transcriptional signatures of aging and somatic mutation patterns","volume":"171","author":"Enge","year":"2017","journal-title":"Cell"},{"key":"2021010313115022300_B23","doi-asserted-by":"crossref","first-page":"R5","DOI":"10.1186\/gb-2012-13-1-r5","article-title":"Uberon, an integrative multi-species anatomy ontology","volume":"13","author":"Mungall","year":"2012","journal-title":"Genome Biol."},{"key":"2021010313115022300_B24","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13326-016-0088-7","article-title":"The Cell Ontology 2016: enhanced content, modularization, and ontology interoperability","volume":"7","author":"Diehl","year":"2016","journal-title":"J. Biomed. Semantics"},{"key":"2021010313115022300_B25","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/nm.2545","article-title":"The lymphatic vasculature in disease","volume":"17","author":"Alitalo","year":"2011","journal-title":"Nat. Med."},{"key":"2021010313115022300_B26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-94-007-7893-1_3","article-title":"Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins","volume":"802","author":"Halper","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"2021010313115022300_B27","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nprot.2014.006","article-title":"Full-length RNA-seq from single cells using Smart-seq2","volume":"9","author":"Picelli","year":"2014","journal-title":"Nat. Protoc."},{"key":"2021010313115022300_B28","doi-asserted-by":"crossref","first-page":"4667","DOI":"10.1038\/s41467-019-12266-7","article-title":"A systematic evaluation of single cell RNA-seq analysis pipelines","volume":"10","author":"Vieth","year":"2019","journal-title":"Nat. Commun."},{"key":"2021010313115022300_B29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3389\/fmicb.2013.00263","article-title":"Pathology of asthma","volume":"4","author":"Kudo","year":"2013","journal-title":"Front. Microbiol."},{"key":"2021010313115022300_B30","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41593-020-0603-0","article-title":"A computational tool (H-MAGMA) for improved prediction of brain-disorder risk genes by incorporating brain chromatin interaction profiles","volume":"23","author":"Sey","year":"2020","journal-title":"Nat. Neurosci."},{"key":"2021010313115022300_B31","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/s41593-019-0382-7","article-title":"A Bayesian framework that integrates multi-omics data and gene networks predicts risk genes from schizophrenia GWAS data","volume":"22","author":"Wang","year":"2019","journal-title":"Nat. Neurosci."},{"key":"2021010313115022300_B32","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/s41587-020-0497-0","article-title":"Single-cell RNA counting at allele and isoform resolution using Smart-seq3","volume":"38","author":"Hagemann-Jensen","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"2021010313115022300_B33","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.cell.2018.09.009","article-title":"Lung Single-Cell signaling interaction map reveals basophil role in macrophage imprinting","volume":"175","author":"Cohen","year":"2018","journal-title":"Cell"},{"key":"2021010313115022300_B34","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/s41596-020-0292-x","article-title":"CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes","volume":"15","author":"Efremova","year":"2020","journal-title":"Nat. Protoc."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/D1\/D862\/35364096\/gkaa1064.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/D1\/D862\/35364096\/gkaa1064.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T18:13:48Z","timestamp":1609697628000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/49\/D1\/D862\/5992286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,19]]},"references-count":34,"journal-issue":{"issue":"D1","published-online":{"date-parts":[[2020,11,19]]},"published-print":{"date-parts":[[2021,1,8]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkaa1064","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1,8]]},"published":{"date-parts":[[2020,11,19]]}}}