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

Genes & Immunity volume 9, pages 161–167 (2008)Cite this article

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.

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Acknowledgements

We thank all the participating family members and many colleagues of the NIDDK IBD Genetics Consortium and collaborating centers who took part in the sample collection and data preparation. We also like to acknowledge the Center for Inherited Diseases Research that performed the genotyping. We also thank Mark Daly for his thoughtful review of the paper and Lisa Wu Datta for her assistance in the preparation of the paper. The National Institute of Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium is funded by the following Grants: DK62431 (SRB), DK62422 and DK62429 (JHC), DK62420 (RHD), DK62432 (JDR), DK62423 (MSS) and DK62413 (KDT). This work was also supported by Burroughs Wellcome (JHC), Crohn's and Colitis Foundation of America (RHD, JHC, TMB), Crohn's and Colitis Foundation of Canada (MSS), NIH General Clinical Research Center Grant RR00052 (SRB) and RR00055 (JHC), the Harvey M and Lynn P Meyerhoff Inflammatory Bowel Disease Center (SRB, TMB), the Atran Foundation (SRB), the W Buford Lewis family (SRB) and the Scaife Family Foundation (RHD).

Author information

Author notes

  1. J H Cho and S R Brant: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Y Y Shugart, M-H Wang, K Zarfas & S R Brant

  2. Department of Medicine, Mount Sinai Hospital Inflammatory Bowel Disease Centre, University of Toronto, Toronto, Canada

    M S Silverberg & A H Steinhart

  3. Department of Medicine, University of Toronto, Toronto, Canada

    M S Silverberg & A H Steinhart

  4. Division of Gastroenterology, Department of Medicine, Hepatology and Nutrition, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    R H Duerr

  5. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    R H Duerr

  6. Division of Medical Genetics and Inflammatory Bowel Disease Center, Cedar-Sinai Medical Center, Los Angeles, CA, USA

    K D Taylor, J I Rotter & L Mei

  7. Department of Medicine and Department of Health Science, The University of Chicago, Chicago, IL, USA

    L P Schumm, G Bromfield & S V Kane

  8. Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada

    A M Griffiths

  9. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    M M Barmada

  10. Section of Gastroenterology, University of Manitoba John Buhler Research Centre, Winnipeg, Manitoba, Canada

    C N Bernstein

  11. Department of Medicine, Harvey M and Lyn P Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    T M Bayless & S R Brant

  12. Service de gastro-entérologie, Centre hospitalier universitaire de Sherbrooke Hôpital, Fleurimont, Quebec, Canada

    D Langelier

  13. Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, Canada

    A Cohen

  14. Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada

    A Bitton

  15. Department of Medicine, Université de Montréal, Montréal Heart Institute, Montreal, Quebec, Canada

    J D Rioux

  16. Department of Medicine and Genetics, Yale University School of Medicine, New Haven, CT, USA

    J H Cho

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  1. Y Y Shugart
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Correspondence to S R Brant.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Shugart, Y., Silverberg, M., Duerr, R. et al. 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 9, 161–167 (2008). https://doi.org/10.1038/sj.gene.6364460

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