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

Academic Article

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 ~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 ~35-fold for CD and ~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.
  • Authors

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    Author List

  • Rioux JD; Silverberg MS; Daly MJ; Steinhart AH; McLeod RS; Griffiths AM; Green T; Brettin TS; Stone V; Bull SB
  • Start Page

  • 1863
  • End Page

  • 1870
  • Volume

  • 66
  • Issue

  • 6