The idiopathic inf lammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are chronic, frequently disabling diseases of the intestines. Segregation analyses, twin concordance, and ethnic differences in familial risks have established that CD and UC are complex, nonMendelian, related genetic disorders. We performed a genome-wide screen using 377 autosomal markers, on 297 CD, UC, or mixed relative pairs from 174 families, 37% Ashkenazim. We observed evidence for linkage at 3q for all families (multipoint logarithm of the odds score (MLod) ‫؍‬ 2.29, P ‫؍‬ 5.7 ؋ 10 ؊4 ), with greatest significance for non-Ashkenazim Caucasians (MLod ‫؍‬ 3.39, P ‫؍‬ 3.92 ؋ 10 ؊5 ), and at chromosome 1p (MLod ‫؍‬ 2.65, P ‫؍‬ 2.4 ؋ 10 ؊4 ) for all families. In a limited subset of mixed families (containing one member with CD and another with UC), evidence for linkage was observed on chromosome 4q (MLod ‫؍‬ 2.76, P ‫؍‬ 1.9 ؋ 10 ؊4 ), especially among Ashkenazim. There was confirmatory evidence for a CD locus, overlapping IBD1, in the pericentromeric region of chromosome 16 (MLod ‫؍‬ 1.69, P ‫؍‬ 2.6 ؋ 10 ؊3 ), particularly among Ashkenazim (MLod ‫؍‬ 1.51, P ‫؍‬ 7.8 ؋ 10 ؊3 ); however, positive MLod scores were observed over a very broad region of chromosome 16. Furthermore, evidence for epistasis between IBD1 and chromosome 1p was observed. Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC.

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: Crohn's disease and ulcerative colitis are related complex genetic disorders producing chronic intestinal inflammation. A susceptibility locus for Crohn's disease, IBDI (inflammatory bowel disease), has been implicated on chromosome 16. To evaluate IBDI in a different population using alternative methodology, we tested markers in the region of IBDI. Seventy-two relative pairs with Crohn's disease only, 23 mixed relative pairs (one relative having Crohn's disease, the other, ulcerative colitis), and 5 relative pairs with ulcerative colitis were genotyped in the region of IBDI. Our population consisted of white Americans, with 29% of families of Ashkenazi Jewish descent. Among the Crohn's disease pairs, we found evidence for linkage at IBDI using multipoint analysis, p = 0.0082. Negative linkage scores were obtained for mixed and ulcerative colitis-only relative pairs. For the entire data set, including mixed relative pairs and relative pairs with ulcerative colitis, there was no significant evidence of linkage. No difference was observed in the evidence of linkage between Jewish and non-Jewish families. Our studies confirm that IBDI represents a susceptibility locus for Crohn's disease, but not ulcerative colitis.

: Crohn's disease and ulcerative colitis are related complex genetic disorders producing chronic intestinal inflammation. A susceptibility locus for Crohn's disease, IBDI (inflammatory bowel disease), has been implicated on chromosome 16. To evaluate IBDI in a different population using alternative methodology, we tested markers in the region of IBDI. Seventy-two relative pairs with Crohn's disease only, 23 mixed relative pairs (one relative having Crohn's disease, the other, ulcerative colitis), and 5 relative pairs with ulcerative colitis were genotyped in the region of IBDI. Our population consisted of white Americans, with 29% of families of Ashkenazi Jewish descent. Among the Crohn's disease pairs, we found evidence for linkage at IBDI using multipoint analysis, p = 0.0082. Negative linkage scores were obtained for mixed and ulcerative colitis-only relative pairs. For the entire data set, including mixed relative pairs and relative pairs with ulcerative colitis, there was no significant evidence of linkage. No difference was observed in the evidence of linkage between Jewish and non-Jewish families. Our studies confirm that IBDI represents a susceptibility locus for Crohn's disease, but not ulcerative colitis.