{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:13:51Z","timestamp":1772626431016,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1005934","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,3,13]],"date-time":"2018-03-13T00:00:00Z","timestamp":1520899200000}}],"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["103258\/Z\/13\/Z"],"award-info":[{"award-number":["103258\/Z\/13\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1005934","type":"journal-article","created":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T13:26:55Z","timestamp":1519910815000},"page":"e1005934","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Shared activity patterns arising at genetic susceptibility loci reveal underlying genomic and cellular architecture of human disease"],"prefix":"10.1371","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5258-793X","authenticated-orcid":true,"given":"J. Kenneth","family":"Baillie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9258-3140","authenticated-orcid":true,"given":"Andrew","family":"Bretherick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9811-0210","authenticated-orcid":true,"given":"Christopher S.","family":"Haley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-9846","authenticated-orcid":true,"given":"Sara","family":"Clohisey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Gray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucile P. A.","family":"Neyton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eli A.","family":"Stahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Tenesa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Ben","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey J.","family":"Faulkner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Lizio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Daub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1772-318X","authenticated-orcid":true,"given":"Masayoshi","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoto","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Lassmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"IIBDGC Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-7302","authenticated-orcid":true,"given":"Damian","family":"Mole","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5435-4750","authenticated-orcid":true,"given":"Vladimir B.","family":"Bajic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-1737","authenticated-orcid":true,"given":"Peter","family":"Heutink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3992-932X","authenticated-orcid":true,"given":"Michael","family":"Rehli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideya","family":"Kawaji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7109-7378","authenticated-orcid":true,"given":"Albin","family":"Sandelin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harukazu","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Satsangi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine A.","family":"Wells","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nir","family":"Hacohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas C.","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihide","family":"Hayashizaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-7243","authenticated-orcid":true,"given":"Piero","family":"Carninci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alistair R. R.","family":"Forrest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Hume","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2018,3,1]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrg3377","article-title":"The heritability of human disease: estimation, uses and abuses","volume":"14","author":"A Tenesa","year":"2013","journal-title":"Nat Rev Genet"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1222794","article-title":"Systematic Localization of Common Disease-Associated Variation in Regulatory DNA","volume":"337","author":"MT Maurano","year":"2012","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature12787","article-title":"An atlas of active enhancers across human cell types and tissues","volume":"507","author":"R Andersson","year":"2014","journal-title":"Nature"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature13835","article-title":"Genetic and epigenetic fine mapping of causal autoimmune disease variants","volume":"518","author":"KK-H Farh","year":"2015","journal-title":"Nature"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1038\/nature13182","article-title":"A promoter-level mammalian expression atlas","volume":"507","author":"A. R. R. Forrest","year":"2014","journal-title":"Nature"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/nmeth.3799","article-title":"Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases","volume":"13","author":"D Marbach","year":"2016","journal-title":"Nat Meth"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1126\/science.1112014","article-title":"The Transcriptional Landscape of the Mammalian Genome","volume":"309","author":"P Carninci","year":"2005","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1126\/science.1259418","article-title":"Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells","volume":"347","author":"E Arner","year":"2015","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/ng.3404","article-title":"Partitioning heritability by functional annotation using genome-wide association summary statistics","volume":"47","author":"HK Finucane","year":"2015","journal-title":"Nat Genet"},{"key":"ref10","first-page":"014241","article-title":"Partitioning heritability by functional category using GWAS summary statistics","author":"HK Finucane","year":"2015","journal-title":"bioRxiv"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ygeno.2010.03.002","article-title":"Functional clustering and lineage markers: insights into cellular differentiation and gene function from large-scale microarray studies of purified primary cell populations","volume":"95","author":"DA Hume","year":"2010","journal-title":"Genomics"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.imbio.2010.05.012","article-title":"Meta-analysis of lineage-specific gene expression signatures in mouse leukocyte populations","volume":"215","author":"NA Mabbott","year":"2010","journal-title":"Immunobiology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/ng.3259","article-title":"Understanding multicellular function and disease with human tissue-specific networks","volume":"47","author":"CS Greene","year":"2015","journal-title":"Nat Genet"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"5890","DOI":"10.1038\/ncomms6890","article-title":"Biological interpretation of genome-wide association studies using predicted gene functions","volume":"6","author":"TH Pers","year":"2015","journal-title":"Nat Commun"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nature22969","article-title":"Fine-mapping inflammatory bowel disease loci to single-variant resolution","volume":"547","author":"H Huang","year":"2017","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","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":"A Franke","year":"2010","journal-title":"Nat Genet"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"e1004714","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":"D Lamparter","year":"2016","journal-title":"PLOS Comput Biol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1056\/NEJM199805283382203","article-title":"Association of Mutations in the Apolipoprotein B Gene with Hypercholesterolemia and the Risk of Ischemic Heart Disease","volume":"338","author":"A Tybj\u00e6rg-Hansen","year":"1998","journal-title":"N Engl J Med"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/83799","article-title":"Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption","volume":"27","author":"M-H Lee","year":"2001","journal-title":"Nat Genet"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/pr.109.002014","article-title":"Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation","volume":"62","author":"CD Klaassen","year":"2010","journal-title":"Pharmacol Rev"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/j.1472-8206.2007.00517.x","article-title":"The expression of the solute carriers NTCP and OCT-1 is regulated by cholesterol in HepG2 cells","volume":"21","author":"V Dias","year":"2007","journal-title":"Fundam Clin Pharmacol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"9983","DOI":"10.1073\/pnas.1314939111","article-title":"OCT1 is a high-capacity thiamine transporter that regulates hepatic steatosis and is a target of metformin","volume":"111","author":"L Chen","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1056\/NEJM199602293340906","article-title":"Metformin","volume":"334","author":"CJ Bailey","year":"1996","journal-title":"N Engl J Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1126\/science.1120781","article-title":"The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin","volume":"310","author":"RJ Shaw","year":"2005","journal-title":"Science"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/bioinformatics\/btr709","article-title":"Robust rank aggregation for gene list integration and meta-analysis","volume":"28","author":"R Kolde","year":"2012","journal-title":"Bioinformatics"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature09906","article-title":"Mapping and analysis of chromatin state dynamics in nine human cell types","volume":"473","author":"J Ernst","year":"2011","journal-title":"Nature"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"D1047","DOI":"10.1093\/nar\/gkr1182","article-title":"GWASdb: a database for human genetic variants identified by genome-wide association studies","volume":"40","author":"MJ Li","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12864-016-2443-6","article-title":"Exploiting biological priors and sequence variants enhances QTL discovery and genomic prediction of complex traits","volume":"17","author":"IM MacLeod","year":"2016","journal-title":"BMC Genomics"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e1000534","DOI":"10.1371\/journal.pgen.1000534","article-title":"Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions","volume":"5","author":"S Raychaudhuri","year":"2009","journal-title":"PLoS Genet"},{"key":"ref30","doi-asserted-by":"crossref","DOI":"10.1186\/s12863-015-0191-2","article-title":"Relative performance of gene- and pathway-level methods as secondary analyses for genome-wide association studies","volume":"16","author":"GL Wojcik","year":"2015","journal-title":"BMC Genet"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e1001273","DOI":"10.1371\/journal.pgen.1001273","article-title":"Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology","volume":"7","author":"EJ Rossin","year":"2011","journal-title":"PLoS Genet"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"A Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"M Kanehisa","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"W749","DOI":"10.1093\/nar\/gkq428","article-title":"GSA-SNP: a general approach for gene set analysis of polymorphisms","volume":"38","author":"D Nam","year":"2010","journal-title":"Nucl Acids Res"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1126\/science.1255074","article-title":"Targeting the host immune response to fight infection","volume":"344","author":"JK Baillie","year":"2014","journal-title":"Science"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/nature06005","article-title":"Unravelling the pathogenesis of inflammatory bowel disease","volume":"448","author":"RJ Xavier","year":"2007","journal-title":"Nature"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/0016-5085(79)90389-5","article-title":"Clinical features and natural history of Crohn\u2019s disease","volume":"77","author":"HS Mekhjian","year":"1979","journal-title":"Gastroenterology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"e1006641","DOI":"10.1371\/journal.pgen.1006641","article-title":"Analysis of the human monocyte-derived macrophage transcriptome and response to lipopolysaccharide provides new insights into genetic aetiology of inflammatory bowel disease","volume":"13","author":"JK Baillie","year":"2017","journal-title":"PLOS Genetics"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.coisb.2017.04.003","article-title":"Treatable traits and therapeutic targets: Goals for systems biology in infectious disease","volume":"2","author":"CD Russell","year":"2017","journal-title":"Current Opinion in Systems Biology"},{"key":"ref40","first-page":"CD003459","article-title":"Methotrexate for induction of remission in refractory Crohn\u2019s disease","author":"JWD McDonald","year":"2014","journal-title":"Cochrane Database Syst Rev"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.cgh.2008.03.014","article-title":"Efficacy and safety of tumor necrosis factor antagonists in Crohn\u2019s disease: meta-analysis of placebo-controlled trials","volume":"6","author":"L Peyrin-Biroulet","year":"2008","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"e81229","DOI":"10.1371\/journal.pone.0081229","article-title":"Network Analysis Reveals Distinct Clinical Syndromes Underlying Acute Mountain Sickness","volume":"9","author":"DP Hall","year":"2014","journal-title":"PLoS ONE"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1005934","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2018,3,13]],"date-time":"2018-03-13T00:00:00Z","timestamp":1520899200000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005934","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T23:29:29Z","timestamp":1570836569000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1005934"}},"subtitle":[],"editor":[{"given":"Sven","family":"Bergmann","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,3,1]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2018,3,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1005934","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/095349","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,1]]}}}