title: The IBD2 locus shows linkage heterogeneity between ulcerative colitis and Crohn disease.
abstract: The IBD2 locus on chromosome 12 has been linked to both Crohn disease (CD) and ulcerative colitis (UC) but has not been detected in some CD-dominated data sets. In the present study, we genotyped 581 relative pairs with inflammatory bowel disease (252 from CD-only families, 138 from UC-only families, and 191 from mixed families containing cases of both CD and UC), using 12 markers spanning the IBD2 locus. A GENEHUNTER-PLUS multipoint LOD score of 3.91 was detected for pairs from UC-only families, compared with 1.66 for CD-only and 1.29 for mixed families. The difference between the LOD scores for UC and CD was significant in two different tests for heterogeneity (P=.0057 for one test and P=.0375 for the other). IBD2 thus appears to make a major contribution to UC susceptibility but to have only a relatively minor effect with regard to CD, for which there may be substantially more locus heterogeneity.
authors.affiliation: Gastroenterology Unit, Nuffield Department of Medicine, Radcliffe Infirmary, University of Oxford, Oxford, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Parkes
authors.forename: M M
authors.initials: MM
authors.lastname: Barmada
authors.forename: J
authors.initials: J
authors.lastname: Satsangi
authors.forename: D E
authors.initials: DE
authors.lastname: Weeks
authors.forename: D P
authors.initials: DP
authors.lastname: Jewell
authors.forename: R H
authors.initials: RH
authors.lastname: Duerr
mesh_terms: D000483:Alleles; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003093:Colitis, Ulcerative / Q000235:genetics*; D003198:Computer Simulation; D003424:Crohn Disease / Q000235:genetics*; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008126:Lod Score; D016555:Matched-Pair Analysis; D018895:Microsatellite Repeats / Q000235:genetics; D009679:Nuclear Family; D012984:Software; D018709:Statistics, Nonparametric; D006113:United Kingdom; D014481:United States