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

Am J Hum Genet. 2000 Jun;66(6):1863-70. doi: 10.1086/302913. Epub 2000 Apr 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Canada
  • Chromosome Mapping
  • Chromosomes, Human / genetics
  • Colitis, Ulcerative / genetics*
  • Crohn Disease / epidemiology
  • Crohn Disease / genetics*
  • Genetic Linkage / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Jews / genetics
  • Lod Score
  • Matched-Pair Analysis
  • Nuclear Family
  • Pedigree
  • Phenotype