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However, no study has specifically investigated the genetic susceptibility loci associated with intestinal involvement in BD. We aimed to identify distinctive genetic susceptibility loci\/genes associated with intestinal involvement in BD and determine their roles in intestinal inflammation as well as their interactions with genes involved in inflammatory bowel disease (IBD). GWAS and validation studies showed intestinal BD-specific associations with an <jats:italic>NAALADL2<\/jats:italic> gene locus (rs3914501, <jats:italic>P<\/jats:italic>\u2009=\u20093.8\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>) and a <jats:italic>YIPF7<\/jats:italic> gene locus (rs6838327, <jats:italic>P<\/jats:italic>\u2009=\u20093.5\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). Validation, haplotype, and pathway analyses showed distinct genetic architectures between intestinal BD and BD without intestinal involvement. Furthermore, network analysis revealed shared pathogenic pathways between intestinal BD and IBD. Gene functional analyses indicated that down-regulation of <jats:italic>NAALADL2<\/jats:italic> and <jats:italic>YIPF7<\/jats:italic> expression was associated with exacerbating intestinal inflammatory responses both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Our results provide new insights into intestinal BD-specific genetic variations, which represents a distinct pathway from BD without intestinal involvement. Functional consequences of the intestinal BD-specific <jats:italic>NAALADL2<\/jats:italic> and <jats:italic>YIPF7<\/jats:italic> expression patterns proved a suggestive association with intestinal inflammation risk, which warrants further validation.<\/jats:p>","DOI":"10.1038\/srep39850","type":"journal-article","created":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T10:19:41Z","timestamp":1483438781000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Identification of genetic susceptibility loci for intestinal Beh\u00e7et\u2019s disease"],"prefix":"10.1038","volume":"7","author":[{"given":"Seung Won","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Suk","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Bum","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Soon","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Won","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Jung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae","family":"Il Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Do Young","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsik","family":"Bang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Ho","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Hee","family":"Cheon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,3]]},"reference":[{"key":"BFsrep39850_CR1","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.1001\/archopht.1982.01030040433013","volume":"100","author":"S Ohno","year":"1982","unstructured":"Ohno, S. et al. 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