[en] Crohn's disease (CD) and ulcerative colitis (UC), the chronic inflammatory bowel diseases (CIBD), are common causes of gastro-intestinal disease in the Western world, with a combined prevalence of 100-200/100,000 (ref. 1). Epidemiological studies, particularly concordance rates in twin pairs and siblings, strongly implicate genetic susceptibility in the pathogenesis of CIBD. In fact, the relative contribution of genetic factors to the pathogenesis of CD may be greater than in schizophrenia, asthma or hypertension, and at least equivalent to that in insulin-dependent diabetes. Systematic screening of the entire human genome now provides a strategy for the identification of susceptibility genes in complex polygenic disorders. We undertook a two-stage genome search for susceptibility genes in inflammatory bowel disease involving 186 affected sibling pairs from 160 nuclear families. We provide strong evidence for the presence of susceptibility loci for both CD and UC on chromosome 3, 7 and 12. We obtained the highest lod score (5.47; P = 2.66 x 10(-7) with the marker D12S83 and lod scores of 3.08 and 2.69 for D7S669 and D3S1573, respectively. Our data suggest that CD and UC are closely related, but distinct, polygenic disorders that share some, but not all, susceptibility genes.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Satsangi, J.
Parkes, M.
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie - Relations académiques et scientifiques (Médecine)
Hashimoto, L.
Kato, N.
Welsh, K.
Terwilliger, J. D.
Lathrop, G. M.
Bellings, Jennifer ; Centre Hospitalier Universitaire de Liège - CHU > Secteur nettoyage
Jewell, D. P.
Language :
English
Title :
Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12.
Publication date :
1996
Journal title :
Nature Genetics
ISSN :
1061-4036
eISSN :
1546-1718
Publisher :
Nature Publishing Group, New York, United States - New York