{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:34:23Z","timestamp":1792694063118,"version":"4.5.0"},"reference-count":44,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>Progress has been made in identifying mutations that confer susceptibility to complex diseases, with the prospect that these genetic risks might be used in determining individual disease risk.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aim:<\/jats:title>\n                  <jats:p>To use Crohn disease (CD) as a model of a common complex disorder, and to develop methods to estimate disease risks using both genetic and environmental risk factors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>The calculations used three independent risk factors: <jats:italic>CARD15<\/jats:italic> genotype (conferring a gene dosage effect on risk), smoking (twofold increased risk for smokers), and residual familial risk (estimating the effect of unidentified genes, after accounting for the contribution of <jats:italic>CARD15<\/jats:italic>). Risks were estimated for high-risk people who are siblings, parents and offspring of a patient with CD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>The CD risk to the sibling of a patient with CD who smokes and carries two <jats:italic>CARD15<\/jats:italic> mutations is approximately 35%, which represents a substantial increase on the population risk of 0.1%. In contrast, the risk to a non-smoking sibling of a patient with CD who carries no <jats:italic>CARD15<\/jats:italic> mutations is 2%. Risks to parents and offspring were lower.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>High absolute risks of CD disease can be obtained by incorporating information on smoking, family history and <jats:italic>CARD15<\/jats:italic> mutations. Behaviour modification through smoking cessation may reduce CD risk in these people.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2007.051672","type":"journal-article","created":{"date-parts":[[2007,7,27]],"date-time":"2007-07-27T21:27:41Z","timestamp":1185571661000},"page":"689-694","source":"Crossref","is-referenced-by-count":39,"title":["Estimating risks of common complex diseases across genetic and environmental factors: the example of Crohn disease"],"prefix":"10.1136","volume":"44","author":[{"given":"C M","family":"Lewis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S C L","family":"Whitwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Forbes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Sanderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C G","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T M","family":"Marteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2007,7,27]]},"reference":[{"key":"2025100521390452000_44.11.689.1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.01.063"},{"key":"2025100521390452000_44.11.689.2","doi-asserted-by":"publisher","DOI":"10.1080\/003655200451207"},{"key":"2025100521390452000_44.11.689.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00385-8"},{"key":"2025100521390452000_44.11.689.4","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320320122"},{"key":"2025100521390452000_44.11.689.5","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/0016-5085(92)90841-L","article-title":"Familial aggregation of inflammatory bowel disease in northern Italy: a multicenter study. 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