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. 2000 Apr 21;66(6):1863–1870. doi: 10.1086/302913

Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci.

J D Rioux 1, M S Silverberg 1, M J Daly 1, A H Steinhart 1, R S McLeod 1, A M Griffiths 1, T Green 1, T S Brettin 1, V Stone 1, S B Bull 1, A Bitton 1, C N Williams 1, G R Greenberg 1, Z Cohen 1, E S Lander 1, T J Hudson 1, K A Siminovitch 1
PMCID: PMC1378042  PMID: 10777714

Abstract

The chronic inflammatory bowel diseases (IBDs)-Crohn disease (CD) and ulcerative colitis (UC)-are idiopathic, inflammatory disorders of the gastrointestinal tract. These conditions have a peak incidence in early adulthood and a combined prevalence of approximately 100-200/100,000. Although the etiology of IBD is multifactorial, a significant genetic contribution to disease susceptibility is implied by epidemiological data revealing a sibling risk of approximately 35-fold for CD and approximately 15-fold for UC. To elucidate the genetic basis for these disorders, we undertook a genomewide scan in 158 Canadian sib-pair families and identified three regions of suggestive linkage (3p, 5q31-33, and 6p) and one region of significant linkage to 19p13 (LOD score 4.6). Higher-density mapping in the 5q31-q33 region revealed a locus of genomewide significance (LOD score 3.9) that contributes to CD susceptibility in families with early-onset disease. Both of these genomic regions contain numerous genes that are important to the immune and inflammatory systems and that provide good targets for future candidate-gene studies.

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Selected References

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