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

JD Rioux, MS Silverberg, MJ Daly, AH Steinhart… - The American Journal of …, 2000 - cell.com
JD Rioux, MS Silverberg, MJ Daly, AH Steinhart, RS McLeod, AM Griffiths, T Green
The American Journal of Human Genetics, 2000cell.com
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 …
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.
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