{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:23:57Z","timestamp":1790490237326,"version":"4.1.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T00:00:00Z","timestamp":1554768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"DOI":"10.3389\/fgene.2019.00318","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T12:55:28Z","timestamp":1554814528000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["A Convergent Study of Genetic Variants Associated With Crohn\u2019s Disease: Evidence From GWAS, Gene Expression, Methylation, eQTL and TWAS"],"prefix":"10.3389","volume":"10","author":[{"given":"Yulin","family":"Dai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangsheng","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongming","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,4,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation.","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1097\/MIB.0000000000000179","article-title":"Two-stage genome-wide methylation profiling in childhood-onset Crohn\u2019s disease implicates epigenetic alterations at the VMP1\/MIR21 and HLA loci.","volume":"20","author":"Adams","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"B3","first-page":"367","article-title":"Environmental risk factors for inflammatory bowel disease.","volume":"9","author":"Ananthakrishnan","year":"2013","journal-title":"Gastroenterol. Hepatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/nrg2918","article-title":"Network medicine: a network-based approach to human disease.","volume":"12","author":"Barabasi","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03621-1","article-title":"Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics.","volume":"9","author":"Barbeira","year":"2018","journal-title":"Nat. Commun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks.","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"B7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2353\/jmoldx.2006.050079","article-title":"Molecular classification of Crohn\u2019s disease and ulcerative colitis patients using transcriptional profiles in peripheral blood mononuclear cells.","volume":"8","author":"Burczynski","year":"2006","journal-title":"J. Mol. Diagn."},{"key":"B8","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1038\/nbt1017","article-title":"Systems biology in drug discovery.","volume":"22","author":"Butcher","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9554","article-title":"Systematic analysis of somatic mutations impacting gene expression in 12 tumour types.","volume":"6","author":"Ding","year":"2015","journal-title":"Nat. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"113","DOI":"10.2147\/JIR.S65979","article-title":"Inflammatory bowel disease: clinical aspects and treatments.","volume":"7","author":"Fakhoury","year":"2014","journal-title":"J. Inflamm. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"4914","DOI":"10.1021\/pr800574c","article-title":"Characterization of the human COP9 signalosome complex using affinity purification and mass spectrometry.","volume":"7","author":"Fang","year":"2008","journal-title":"J. Proteome Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/ng.717","article-title":"Genome-wide meta-analysis increases to 71 the number of confirmed Crohn\u2019s disease susceptibility loci.","volume":"42","author":"Franke","year":"2010","journal-title":"Nat. Genet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.1093\/bioinformatics\/btt487","article-title":"RDAVIDWebService: a versatile R interface to DAVID.","volume":"29","author":"Fresno","year":"2013","journal-title":"Bioinformatics"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1097\/MIB.0000000000000393","article-title":"Heritability in inflammatory bowel disease: from the first twin study to genome-wide association studies.","volume":"21","author":"Gordon","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"B15","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1038\/nature24277","article-title":"Genetic effects on gene expression across human tissues.","volume":"550","year":"2017","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/s41588-018-0092-1","article-title":"Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights.","volume":"50","author":"Gusev","year":"2018","journal-title":"Nat. Genet."},{"key":"B17","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1365-2443.2007.01049.x","article-title":"COP9 signalosome subunit 5 (CSN5\/Jab1) regulates the development of the Drosophila immune system: effects on Cactus, Dorsal and hematopoiesis.","volume":"12","author":"Harari-Steinberg","year":"2007","journal-title":"Genes Cells"},{"key":"B18","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.ajhg.2013.03.022","article-title":"Sherlock: detecting gene-disease associations by matching patterns of expression QTL and GWAS.","volume":"92","author":"He","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"B19","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1101\/gr.178855.114","article-title":"The discovery of integrated gene networks for autism and related disorders.","volume":"25","author":"Hormozdiari","year":"2015","journal-title":"Genome Res."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1093\/database\/bay121","article-title":"ANCO-GeneDB: annotations and comprehensive analysis of candidate genes for alcohol, nicotine, cocaine and opioid dependence.","volume":"2018","author":"Hu","year":"2018","journal-title":"Database"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2017.00084","article-title":"More is better: recent progress in multi-omics data integration methods.","volume":"8","author":"Huang","year":"2017","journal-title":"Front. Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1038\/nature12170","article-title":"Negligible impact of rare autoimmune-locus coding-region variants on missing heritability.","volume":"498","author":"Hunt","year":"2013","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sby085","article-title":"Mega-analysis of odds ratio: a convergent method for a deep understanding of the genetic evidence in schizophrenia.","author":"Jia","year":"2018","journal-title":"Schizophr. Bull."},{"key":"B24","doi-asserted-by":"publisher","first-page":"D915","DOI":"10.1093\/nar\/gkw902","article-title":"SZGR 2.0: a one-stop shop of schizophrenia candidate genes.","volume":"45","author":"Jia","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-1015","article-title":"Key regulators in prostate cancer identified by co-expression module analysis.","volume":"15","author":"Jiang","year":"2014","journal-title":"BMC Genomics"},{"key":"B26","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1093\/bib\/bbv107","article-title":"Systematic dissection of dysregulated transcription factor-miRNA feed-forward loops across tumor types.","volume":"17","author":"Jiang","year":"2016","journal-title":"Brief. Bioinform."},{"key":"B27","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/nature11582","article-title":"Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.","volume":"491","author":"Jostins","year":"2012","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nature10209","article-title":"Genetics and pathogenesis of inflammatory bowel disease.","volume":"474","author":"Khor","year":"2011","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004714","article-title":"Fast and rigorous computation of gene and pathway scores from SNP-Based summary statistics.","volume":"12","author":"Lamparter","year":"2016","journal-title":"PLoS Comput. Biol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1101\/gr.118992.110","article-title":"Prioritizing candidate disease genes by network-based boosting of genome-wide association data.","volume":"21","author":"Lee","year":"2011","journal-title":"Genome Res."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/celldisc.2016.25","article-title":"Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers.","volume":"2","author":"Lee","year":"2016","journal-title":"Cell Discov."},{"key":"B32","doi-asserted-by":"publisher","first-page":"D1121","DOI":"10.1093\/nar\/gkx1076","article-title":"Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics.","volume":"46","author":"Li","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/ng.3359","article-title":"Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.","volume":"47","author":"Liu","year":"2015","journal-title":"Nat. Genet."},{"key":"B34","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1053\/j.gastro.2004.01.063","article-title":"Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences.","volume":"126","author":"Loftus","year":"2004","journal-title":"Gastroenterology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/ng.3761","article-title":"Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7.","volume":"49","author":"Luo","year":"2017","journal-title":"Nat. Genet."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1038\/ng.3936","article-title":"Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn\u2019s disease.","volume":"49","author":"Marigorta","year":"2017","journal-title":"Nat. Genet."},{"key":"B37","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ni1514","article-title":"COP9 signalosome subunit 8 is essential for peripheral T cell homeostasis and antigen receptor-induced entry into the cell cycle from quiescence.","volume":"8","author":"Menon","year":"2007","journal-title":"Nat. Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1261\/rna.048132.114","article-title":"Concordant dysregulation of miR-5p and miR-3p arms of the same precursor microRNA may be a mechanism in inducing cell proliferation and tumorigenesis: a lung cancer study.","volume":"21","author":"Mitra","year":"2015","journal-title":"RNA"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0522-9","article-title":"Weak sharing of genetic association signals in three lung cancer subtypes: evidence at the SNP, gene, regulation, and pathway levels.","volume":"10","author":"O\u2019Brien","year":"2018","journal-title":"Genome Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1084\/jem.20070725","article-title":"Targeted inactivation of the COP9 signalosome impairs multiple stages of T cell development.","volume":"205","author":"Panattoni","year":"2008","journal-title":"J. Exp. Med."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz138","article-title":"deTS: tissue-specific enrichment analysis to decode tissue specificity.","author":"Pei","year":"","journal-title":"Bioinformatics"},{"key":"B42","doi-asserted-by":"publisher","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":"","journal-title":"BMC Genomics"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies.","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1038\/ng.952","article-title":"Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease.","volume":"43","author":"Rivas","year":"2011","journal-title":"Nat. Genet."},{"key":"B45","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a software environment for integrated models of biomolecular interaction networks.","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bby020","article-title":"Distinct telomere length and molecular signatures in seminoma and non-seminoma of testicular germ cell tumor.","author":"Sun","year":"2018","journal-title":"Brief Bioinform."},{"key":"B47","doi-asserted-by":"publisher","first-page":"D362","DOI":"10.1093\/nar\/gkw937","article-title":"The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible.","volume":"45","author":"Szklarczyk","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13507","article-title":"Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.","volume":"7","author":"Ventham","year":"2016","journal-title":"Nat. Commun."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1001","article-title":"Genome-wide association studies in Crohn\u2019s disease: past, present and future.","volume":"7","author":"Verstockt","year":"2018","journal-title":"Clin. Transl. Immunol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.ajhg.2017.06.005","article-title":"10 years of GWAS discovery: biology, function, and translation.","volume":"101","author":"Visscher","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"B51","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.192.Supp.133.15","article-title":"COP9 regulates intestinal microbial ecology and susceptibility to colitis (MUC4P.839).","volume":"192","author":"Wang","year":"2014","journal-title":"J. Immunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2591","DOI":"10.1093\/bioinformatics\/btv150","article-title":"EW_dmGWAS: edge-weighted dense module search for genome-wide association studies and gene expression profiles.","volume":"31","author":"Wang","year":"2015","journal-title":"Bioinformatics"},{"key":"B53","article-title":"An integrative genomics approach for identifying novel functional consequences of PBRM1 truncated mutations in clear cell renal cell carcinoma (ccRCC).","author":"Wang","year":"2016","journal-title":"BMC Genomics"},{"key":"B54","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev.cellbio.19.111301.112449","article-title":"The COP9 signalosome.","volume":"19","author":"Wei","year":"2003","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.tibs.2008.09.004","article-title":"The COP9 signalosome: more than a protease.","volume":"33","author":"Wei","year":"2008","journal-title":"Trends Biochem. Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1038\/nature08979","article-title":"Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.","volume":"464","author":"Craddock","year":"2010","journal-title":"Nature"},{"key":"B57","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/ibd.20110","article-title":"Genome-wide gene expression differences in Crohn\u2019s disease and ulcerative colitis from endoscopic pinch biopsies: insights into distinctive pathogenesis.","volume":"13","author":"Wu","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"key":"B58","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1093\/ije\/dyi130","article-title":"How many genes underlie the occurrence of common complex diseases in the population?","volume":"34","author":"Yang","year":"2005","journal-title":"Int. J. Epidemiol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1093\/bioinformatics\/btu811","article-title":"Identifying cancer-related microRNAs based on gene expression data.","volume":"31","author":"Zhao","year":"2015","journal-title":"Bioinformatics"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fgene.2019.00318\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T15:04:35Z","timestamp":1694790275000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fgene.2019.00318\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,9]]},"references-count":59,"alternative-id":["10.3389\/fgene.2019.00318"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2019.00318","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,9]]},"article-number":"318"}}