{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:49:21Z","timestamp":1790804961076,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017291","name":"Health and Social Care","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017291","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Crohn\u2019s disease (CD) is highly heterogenous and may be complicated by stricturing behavior. Personalized prediction of stricturing will inform management. We aimed to create a stricturing risk stratification model using genomic\/clinical data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Exome sequencing was performed on CD patients, and phenotype data retrieved. Biallelic variants in NOD2 were identified. NOD2 was converted into a per-patient deleteriousness metric (\u201cGenePy\u201d). Using training data, patients were stratified into risk groups for fibrotic stricturing using NOD2. Findings were validated in a testing data set. Models were modified to include disease location at diagnosis. Cox proportional hazards assessed performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six hundred forty-five patients were included (373 children and 272 adults); 48 patients fulfilled criteria for monogenic NOD2-related disease (7.4%), 24 of whom had strictures. NOD2 GenePy scores stratified patients in training data into 2 risk groups. Within testing data, 30 of 161 patients (18.6%) were classified as high-risk based on the NOD2 biomarker, with stricturing in 17 of 30 (56.7%). In the low-risk group, 28 of 131 (21.4%) had stricturing behavior. Cox proportional hazards using the NOD2 risk groups demonstrated a hazard ratio (HR) of 2.092 (P\u2005=\u20052.4\u2005\u00d7\u200510-5), between risk groups. Limiting analysis to patients diagnosed aged\u2005&amp;lt;\u200518-years improved performance (HR-3.164, P\u2005=\u20051\u2005\u00d7\u200510-6). Models were modified to include disease location, such as terminal ileal (TI) disease or not. Inclusion of NOD2 risk groups added significant additional utility to prediction models. High-risk group pediatric patients presenting with TI disease had a HR of 4.89 (P\u2005=\u20052.3\u2005\u00d7\u200510-5) compared with the low-risk group patients without TI disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A NOD2 genomic biomarker predicts stricturing risk, with prognostic power improved in pediatric-onset CD. Implementation into a clinical setting can help personalize management.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ibd\/izac205","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T14:49:02Z","timestamp":1664203742000},"page":"511-521","source":"Crossref","is-referenced-by-count":14,"title":["Prediction of Crohn\u2019s Disease Stricturing Phenotype Using a<i>NOD2-<\/i>derived Genomic Biomarker"],"prefix":"10.1093","volume":"29","author":[{"given":"James J","family":"Ashton","sequence":"first","affiliation":[{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton , Southampton , UK"},{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton , Southampton , UK"},{"name":"NIHR Southampton Biomedical Research Centre, University Hospital Southampton , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imogen S","family":"Stafford","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton , Southampton , UK"},{"name":"Institute for Life Sciences, University of Southampton , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Kellermann","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor G","family":"Seaby","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J R Fraser","family":"Cummings,","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital Southampton , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy A F","family":"Coelho","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Batra","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadeem A","family":"Afzal","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R Mark","family":"Beattie","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Southampton Children\u2019s Hospital , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Ennis","sequence":"additional","affiliation":[{"name":"Department of Human Genetics and Genomic Medicine, University of Southampton , Southampton , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"2023040316443075500_","first-page":"56","article-title":"Personalising medicine in inflammatory bowel disease\u2014current and future perspectives","volume-title":"Translational Pediatrics","author":"Ashton","year":"2019"},{"key":"2023040316443075500_","first-page":"527","article-title":"Pathway paradigms revealed from the genetics of inflammatory bowel 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