Confirmation of a Susceptibility Locus for Crohnʼs Disease on Chromosome 16

Abstract

: 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.

Identification of novel susceptibility loci for inflammatory bowel disease on chromosomes 1p, 3q, and 4q: Evidence for epistasis between 1p and IBD1

“…Two previous genome-wide screens have identified susceptibility loci on chromosome 16 (16) in CD families (subsequently confirmed) (17)(18)(19) and loci on chromosomes 12, 7, and 3p in all inflammatory bowel disease families (20). The CD locus on chromosome 16, IBD1 (16), and the inflammatory bowel disease locus on chromosome 12 (20) were reported to have estimated locus-specific s of 1.3 and 2.0, respectively.…”

“…This region subsequently has been confirmed for CD but not UC (17)(18)(19). A separate genome-wide screen (89 sibling pairs undergoing the initial, genome-wide screen with 260 autosomal markers and 97 pairs used for replication) was performed on families from the United Kingdom with all inflammatory bowel disease phenotypes (UC, CD, and mixed families) (20).…”