{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:04:08Z","timestamp":1790895848939,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008359","name":"Dutch Digestive Foundation","doi-asserted-by":"crossref","award":["D16-14"],"award-info":[{"award-number":["D16-14"]}],"id":[{"id":"10.13039\/501100008359","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Inflammatory bowel disease [IBD] phenotypes are very heterogeneous between patients, and current clinical and molecular classifications do not accurately predict the course that IBD will take over time. Genetic determinants of disease phenotypes remain largely unknown but could aid drug development and allow for personalised management. We used genetic risk scores [GRS] to disentangle the genetic contributions to IBD phenotypes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Clinical characteristics and imputed genome-wide genetic array data of patients with IBD were obtained from two independent cohorts [cohort A, n\u2005=\u20051097; cohort B, n\u2005=\u20052156]. Genetic risk scoring [GRS] was used to assess genetic aetiology shared across traits and IBD phenotypes. Significant GRS\u2013phenotype (false-discovery rate [FDR] corrected p\u2005&amp;lt;0.05) associations identified in cohort A were put forward for replication in cohort B.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Crohn\u2019s disease [CD] GRS were associated with fibrostenotic CD [R2\u2005=\u20057.4%, FDR\u2005=\u20050.02] and ileocaecal resection [R2\u2005=\u20054.1%, FDR\u2005=\u20051.6E-03], and this remained significant after correcting for previously identified clinical and genetic risk factors. Ulcerative colitis [UC] GRS [R2\u2005=\u20057.1%, FDR\u2005=\u20050.02] and primary sclerosing cholangitis [PSC] GRS [R2\u2005=\u20053.6%, FDR\u2005=\u20050.03] were associated with colonic CD, and these two associations were largely driven by genetic variation in MHC. We also observed pleiotropy between PSC genetic risk and smoking behaviour [R2\u2005=\u20051.7%, FDR\u2005=\u20050.04].<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Patients with a higher genetic burden of CD are more likely to develop fibrostenotic disease and undergo ileocaecal resection, whereas colonic CD shares genetic aetiology with PSC and UC that is largely driven by variation in MHC. These results further our understanding of specific IBD phenotypes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaa223","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T12:11:24Z","timestamp":1603887084000},"page":"930-937","source":"Crossref","is-referenced-by-count":12,"title":["Genetic Risk Scores Identify Genetic Aetiology of Inflammatory Bowel Disease Phenotypes"],"prefix":"10.1093","volume":"15","author":[{"given":"M D","family":"Voskuil","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"},{"name":"Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L M","family":"Spekhorst","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K W J","family":"van der Sloot","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"},{"name":"Department of Epidemiology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B H","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C J","family":"van der Woude","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus Medical Centre, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Hoentjen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6981-6516","authenticated-orcid":false,"given":"M J","family":"Pierik","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A E","family":"van der Meulen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N K H","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Vrije Universiteit Amsterdam, AG&M Research Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"L\u00f6wenberg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam University Medical Centres, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E A M","family":"Festen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"},{"name":"Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R K","family":"Weersma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,11,6]]},"reference":[{"key":"2021062213004429200_CIT0001","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1016\/S0140-6736(16)31711-1","article-title":"Crohn\u2019s disease","volume":"389","author":"Torres","year":"2017","journal-title":"Lancet"},{"key":"2021062213004429200_CIT0002","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1016\/S0140-6736(16)32126-2","article-title":"Ulcerative colitis","volume":"389","author":"Ungaro","year":"2017","journal-title":"Lancet"},{"key":"2021062213004429200_CIT0003","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/s41575-019-0118-x","article-title":"Redefining the IBDs using genome-scale molecular phenotyping","volume":"16","author":"Furey","year":"2019","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2021062213004429200_CIT0004","doi-asserted-by":"crossref","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":"2021062213004429200_CIT0005","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/ng.3760","article-title":"Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease","volume":"49","author":"de Lange","year":"2017","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0006","doi-asserted-by":"crossref","first-page":"e1001283","DOI":"10.1371\/journal.pgen.1001283","article-title":"A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn\u2019s disease and celiac disease","volume":"7","author":"Festen","year":"2011","journal-title":"PLoS Genet"},{"key":"2021062213004429200_CIT0007","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nrg3502","article-title":"Genetic insights into common pathways and complex relationships among immune-mediated diseases","volume":"14","author":"Parkes","year":"2013","journal-title":"Nat Rev Genet"},{"key":"2021062213004429200_CIT0008","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1053\/gast.1996.v111.pm8780563","article-title":"Clinical characteristics of Crohn\u2019s disease in 72 families","volume":"111","author":"Colombel","year":"1996","journal-title":"Gastroenterology"},{"key":"2021062213004429200_CIT0009","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/S0016-5085(03)00385-8","article-title":"Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics","volume":"124","author":"Halfvarson","year":"2003","journal-title":"Gastroenterology"},{"key":"2021062213004429200_CIT0010","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0140-6736(15)00465-1","article-title":"Inherited determinants of Crohn\u2019s disease and ulcerative colitis phenotypes: a genetic association study","volume":"387","author":"Cleynen","year":"2016","journal-title":"Lancet"},{"key":"2021062213004429200_CIT0011","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/nature08185","article-title":"Common polygenic variation contributes to risk of schizophrenia and bipolar disorder","volume":"460","author":"Purcell","year":"2009","journal-title":"Nature"},{"key":"2021062213004429200_CIT0012","doi-asserted-by":"crossref","first-page":"e1003348","DOI":"10.1371\/journal.pgen.1003348","article-title":"Power and predictive accuracy of polygenic risk scores","volume":"9","author":"Dudbridge","year":"2013","journal-title":"PLoS Genet"},{"key":"2021062213004429200_CIT0013","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12876-018-0917-5","article-title":"The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1","volume":"19","author":"Imhann","year":"2019","journal-title":"BMC Gastroenterol"},{"key":"2021062213004429200_CIT0014","doi-asserted-by":"crossref","first-page":"e016695","DOI":"10.1136\/bmjopen-2017-016695","article-title":"Cohort profile: design and first results of the Dutch IBD Biobank: a prospective, nationwide biobank of patients with inflammatory bowel disease","volume":"7","author":"Spekhorst","year":"2017","journal-title":"BMJ Open"},{"key":"2021062213004429200_CIT0015","doi-asserted-by":"crossref","first-page":"5A","DOI":"10.1155\/2005\/269076","article-title":"Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology","volume":"19[","author":"Silverberg","year":"2005","journal-title":"Can J Gastroenterol"},{"key":"2021062213004429200_CIT0016","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/ng.3679","article-title":"Reference-based phasing using the Haplotype Reference Consortium panel","volume":"48","author":"Loh","year":"2016","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0017","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"The 1000 Genomes Project Consortium","year":"2015","journal-title":"Nature"},{"key":"2021062213004429200_CIT0018","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"key":"2021062213004429200_CIT0019","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/ng.3176","article-title":"High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis","volume":"47","author":"Goyette","year":"2015","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0020","article-title":"Practical use of methods for imputation of HLA alleles from SNP genotype data","author":"Motyer","year":"2016","journal-title":"BioRxiv"},{"key":"2021062213004429200_CIT0021","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng.3745","article-title":"Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease","volume":"49","author":"Ji","year":"2017","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0022","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/ng.582","article-title":"Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci","volume":"42","author":"Stahl","year":"2010","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0023","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1056\/NEJMoa0906312","article-title":"A large-scale, consortium-based genomewide association study of asthma","volume":"363","author":"Moffatt","year":"2010","journal-title":"N Engl J Med"},{"key":"2021062213004429200_CIT0024","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41431-019-0520-4","article-title":"Immunochip meta-analysis in European and Argentinian populations identifies two novel genetic loci associated with celiac disease","volume":"28","author":"Rica\u00f1o-Ponce","year":"2020","journal-title":"Eur J Hum Genet"},{"key":"2021062213004429200_CIT0025","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S2213-2600(17)30387-9","article-title":"Genetic variants associated with susceptibility to idiopathic pulmonary fibrosis in people of European ancestry: a genome-wide association study","volume":"5","author":"Allen","year":"2017","journal-title":"Lancet Respir Med"},{"key":"2021062213004429200_CIT0026","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41588-018-0203-z","article-title":"Genome-wide association analyses identify 39 new susceptibility loci for diverticular disease","volume":"50","author":"Maguire","year":"2018","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0027","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/ng.571","article-title":"Genome-wide meta-analyses identify multiple loci associated with smoking behavior","volume":"42","author":"Furberg","year":"2010","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0028","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/ng.3755","article-title":"Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn\u2019s disease","volume":"49","author":"Lee","year":"2017","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0029","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1038\/ng.3949","article-title":"Identification of 153 new loci associated with heel bone mineral density and functional involvement of GPC6 in osteoporosis","volume":"49","author":"Kemp","year":"2017","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0030","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/s41467-017-02662-2","article-title":"Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels","volume":"9","author":"Jiang","year":"2018","journal-title":"Nat Commun"},{"key":"2021062213004429200_CIT0031","doi-asserted-by":"crossref","first-page":"giz082","DOI":"10.1093\/gigascience\/giz082","article-title":"PRSice-2: Polygenic Risk Score software for biobank-scale data","volume":"8","author":"Choi","year":"2019","journal-title":"Gigascience"},{"key":"2021062213004429200_CIT0032","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/ng.2616","article-title":"Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis","volume":"45","author":"Liu","year":"2013","journal-title":"Nat Genet"},{"key":"2021062213004429200_CIT0033","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1136\/gutjnl-2016-312135","article-title":"Interplay of host genetics and gut microbiota underlying the onset and clinical presentation of inflammatory bowel disease","volume":"67","author":"Imhann","year":"2018","journal-title":"Gut"},{"key":"2021062213004429200_CIT0034","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1177\/2050640618761703","article-title":"Association between smoking and risk of primary sclerosing cholangitis: A systematic review and meta-analysis","volume":"6","author":"Wijarnpreecha","year":"2018","journal-title":"United European Gastroenterol J"}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ecco-jcc\/advance-article-pdf\/doi\/10.1093\/ecco-jcc\/jjaa223\/36647991\/jjaa223.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/15\/6\/930\/38756709\/jjaa223.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/15\/6\/930\/38756709\/jjaa223.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T13:04:02Z","timestamp":1624367042000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/15\/6\/930\/5957220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,6]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2020,11,6]]},"published-print":{"date-parts":[[2021,6,22]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjaa223","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,6,1]]},"published":{"date-parts":[[2020,11,6]]}}}