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

Genes Immun. 2008 Mar;9(2):161-7. doi: 10.1038/sj.gene.6364460. Epub 2008 Jan 31.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 1 / genetics*
  • Chromosomes, Human, Pair 13 / genetics*
  • Chromosomes, Human, Pair 3 / genetics*
  • Colitis, Ulcerative / epidemiology
  • Colitis, Ulcerative / genetics
  • Crohn Disease / epidemiology
  • Crohn Disease / genetics*
  • Female
  • Genetic Linkage / genetics
  • Genetic Markers / genetics
  • Humans
  • Jews / genetics*
  • Lod Score
  • Male
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics*
  • Quantitative Trait Loci / genetics

Substances

  • Genetic Markers