An SNP linkage scan identifies significant Crohn's disease loci on chromosomes 13q13.3 and, in Jewish families, on 1p35.2 and 3q29

作者：Shugart Y Y; Silverberg M S; Duerr R H; Taylor K D; Wang M H; Zarfas K; Schumm L P; Bromfield G; Steinhart A H; Griffiths A M; Kane S V; Barmada M M; Rotter J I; Mei L; Bernstein C N; Bayless T M; Langelier D; Cohen A; Bitton A; Rioux J D; Cho J H; Brant S R^*

来源：Genes and Immunity, 2008, 9(2): 161-167.

DOI：10.1038/sj.gene.6364460

• Crohn's disease
• ulcerative colitis
• linkage
• genetics

Inflammatory bowel disease (IBD) is a complex genetic disorder of two major phenotypes, Crohn's disease (CD) and ulcerative colitis (UC), with increased risk in Ashkenazi Jews. Twelve genome-wide linkage screens have identified multiple loci, but these screens have been of modest size and have used low-density microsatellite markers. We, therefore, performed a high-density single-nucleotide polymorphism (SNP) genome-wide linkage study of 993 IBD multiply affected pedigrees (25% Jewish ancestry) that contained 1709 IBD-affected relative pairs, including 919 CD-CD pairs and 312 UC-UC pairs. We identified a significant novel CD locus on chromosome 13p13.3 (peak logarithm of the odds (LOD) score = 3.98) in all pedigrees, significant linkage evidence on chromosomes 1p35.1 (peak LOD score = 3.5) and 3q29 (peak LOD score = 3.19) in Jewish CD pedigrees, and suggestive loci for Jewish IBD on chromosome 10q22 (peak LOD score = 2.57) and Jewish UC on chromosome 2q24 (peak LOD score = 2.69). Nominal or greater linkage evidence was present for most previously designated IBD loci (IBD1-9), notably, IBD1 for CD families at chromosome 16q12.1 (peak LOD score = 4.86) and IBD6 in non-Jewish UC families at chromosome 19p12 (peak LOD score = 2.67). This study demonstrates the ability of high information content adequately powered SNP genome-wide linkage studies to identify loci not observed in multiple microsatellite-based studies in smaller cohorts.

• 出版日期2008-3
• 单位McGill