1. ¹Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
2. ²Department of Medicine, Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, Toronto, Canada
3. ³Department of Medicine, University of Toronto, Toronto, Canada
4. ⁴Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA
5. ⁵Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
6. ⁶Division of Medical Genetics and Inflammatory Bowel Disease Center, Cedar-Sinai Medical Center, Los Angeles, CA, USA
7. ⁷Department of Medicine and Department of Health Science, The University of Chicago, Chicago, IL, USA
8. ⁸Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada
9. ⁹Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
10. ¹⁰Section of Gastroenterology, University of Manitoba John Buhler Research Centre, Winnipeg, Manitoba, Canada
11. ¹¹Department of Medicine, Harvey M and Lyn P Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
12. ¹²Service de gastro-entérologie, Centre hospitalier universitaire de Sherbrooke Hôpital, Fleurimont, Quebec, Canada
13. ¹³Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada
14. ¹⁴Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada
15. ¹⁵Department of Medicine, Université de Montréal, Montréal Heart Institute, Montreal, Quebec, Canada
16. ¹⁶Department of Medicine and Genetics, Yale University School of Medicine, New Haven, CT, USA

Correspondence: Dr SR Brant, Department of Medicine, School of Medicine and Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 1503 East Jefferson Street, B136, Baltimore, MD 21231, USA. E-mail: sbrant@jhmi.edu

¹⁷These authors contributed equally to this work.

Received 13 November 2007; Accepted 14 December 2007; Published online 31 January 2008.

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.