{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T04:34:02Z","timestamp":1761712442838,"version":"build-2065373602"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100011684","name":"Crohn\u2019s & Colitis Foundation","doi-asserted-by":"crossref","award":["881999"],"award-info":[{"award-number":["881999"]}],"id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Inflammatory bowel disease (IBD) often affects multiple relatives, pointing toward shared genetic and\/or environmental factors. This study evaluates the importance of known IBD risk variants, and of genetic determinants of smoking in such multiplex families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied 65 IBD multiplex families, comprising 146 Crohn\u2019s disease (CD), 33 ulcerative colitis (UC), and 111 unaffected relatives. All families had at least 3 affected first-degree relatives. Common variant and rare variant polygenic risk scores (PRS and rvPRS) in these individuals were calculated and compared to 2040 sporadic IBD cases (1198 CD, 842 UC) and 598 unrelated controls. Associations for PRS, rvPRS, and smoking PRS were assessed using univariable and multivariable models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Within multiplex families, unaffected relatives had lower PRS than affected relatives (P\u2009=\u20090.01), but still higher scores than unrelated controls (P\u2009=\u20090.01). Interestingly, rvPRS did not differ between affected and unaffected relatives. PRS and rvPRS showed substantial heterogeneity across families; for example 10 families (2 for rvPRS) had PRS below unrelated controls, while 27 (6 for rvPRS) scored above sporadic cases. No correlation was found between PRS and rvPRS at the individual or family level. Smoking-related PRS were not associated with familial IBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multiplex IBD families show diverse genetic architecture, with almost half showing a high burden of common and\/or rare risk variants. While genetic predispositions to smoking influences IBD risk in sporadic cases, it provides limited insights into familial IBD. These findings highlight the genetic complexity within multiplex families and the need for tailored research approaches such as risk stratification and genetic screening strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaf165","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T11:46:31Z","timestamp":1756986391000},"source":"Crossref","is-referenced-by-count":0,"title":["Unravelling the genetic architecture of inflammatory bowel disease multiplex families with rare and common variant polygenic risk scores"],"prefix":"10.1093","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2791-2010","authenticated-orcid":false,"given":"Deborah S","family":"Jans","sequence":"first","affiliation":[{"name":"Laboratory for Complex Genetics, Department of Human Genetics, KU Leuven , 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Leuven,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1492-0716","authenticated-orcid":false,"given":"Marc","family":"Ferrante","sequence":"additional","affiliation":[{"name":"Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven , Leuven,","place":["Belgium"]},{"name":"Department of Gastroenterology and Hepatology, University Hospitals Leuven , Leuven,","place":["Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o","family":"Sabino","sequence":"additional","affiliation":[{"name":"Translational Research in Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven , Leuven,","place":["Belgium"]},{"name":"Department of Gastroenterology and Hepatology, University Hospitals Leuven , 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