{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:20:53Z","timestamp":1780647653740,"version":"3.54.1"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"R2","license":[{"start":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T00:00:00Z","timestamp":1564531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Institute of Health Center for Multi- and Trans-Ethnic Mapping of Mendelian and Complex Diseases","award":["5U01 HG009080"],"award-info":[{"award-number":["5U01 HG009080"]}]},{"DOI":"10.13039\/100005492","name":"Stanford University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000092","name":"National Library of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000092","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Human Genome Research Institute of the National Institutes of Health","award":["R01HG010140"],"award-info":[{"award-number":["R01HG010140"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Complex diseases such as inflammatory bowel disease (IBD), which consists of ulcerative colitis and Crohn\u2019s disease, are a significant medical burden\u201470\u2009000 new cases of IBD are diagnosed in the United States annually. In this review, we examine the history of genetic variant discovery in complex disease with a focus on IBD. We cover methods that have been applied to microsatellite, common variant, targeted resequencing and whole-exome and -genome data, specifically focusing on the progression of technologies towards rare-variant discovery. The inception of these methods combined with better availability of population level variation data has led to rapid discovery of IBD-causative and\/or -associated variants at over 200 loci; over time, these methods have grown exponentially in both power and ascertainment to detect rare variation. We highlight rare-variant discoveries critical to the elucidation of the pathogenesis of IBD, including those in NOD2, IL23R, CARD9, RNF186 and ADCY7. We additionally identify the major areas of rare-variant discovery that will evolve in the coming years. A better understanding of the genetic basis of IBD and other complex diseases will lead to improved diagnosis, prognosis, treatment and surveillance.<\/jats:p>","DOI":"10.1093\/hmg\/ddz189","type":"journal-article","created":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T15:08:34Z","timestamp":1564067314000},"page":"R162-R169","source":"Crossref","is-referenced-by-count":26,"title":["Rare and common variant discovery in complex disease: the IBD case study"],"prefix":"10.1093","volume":"28","author":[{"given":"Guhan R","family":"Venkataraman","sequence":"first","affiliation":[{"name":"Department of Biomedical Data Science, School of Medicine, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel A","family":"Rivas","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Science, School of Medicine, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,31]]},"reference":[{"key":"2019122310522504600_ref1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nature10209","article-title":"Genetics and pathogenesis of inflammatory bowel disease","volume":"474","author":"Khor","year":"2011","journal-title":"Nature"},{"key":"2019122310522504600_ref2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1053\/j.gastro.2016.12.004","article-title":"Inflammatory bowel disease 2017: innovations and changing paradigms","volume":"152","author":"Colombel","year":"2017","journal-title":"Gastroenterology"},{"key":"2019122310522504600_ref3","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izz104","article-title":"The cost of inflammatory bowel disease: an initiative from the Crohn\u2019s & Colitis Foundation","author":"Park","year":"2019","journal-title":"Inflamm. 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