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New links to the pathogenesis of Crohn disease provided by genome-wide association scans

Nature Reviews Genetics volume 9, pages 9–14 (2008)Cite this article

Abstract

Genome-wide association scans (GWAS) using large case–control samples and several hundred thousand genetic markers have uncovered at least ten new genomic regions associated with susceptibility to Crohn disease, a chronic inflammatory bowel disorder. The new loci include genes with diverse roles in the immune response and several gene deserts, which may contain regulatory sequences or encode novel functional transcripts. The results so far suggest that genome scans may re-define our ideas on the nature of causal variants in complex disease.

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Figure 1: A genome-wide association scan.
Figure 2: New genes and functional pathways for Crohn disease.

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Acknowledgements

I would like to thank my colleagues from King's College, London, for comments on this manuscript, and the UK Inflammatory Bowel Disease Genetics Consortium and the Wellcome Trust Case Control Consortium, with whom I worked on the genome-wide scan in Crohn disease.

Author information

Authors and Affiliations

  1. Christopher G. Mathew is at the Division of Genetics and Molecular Medicine, King's College London School of Medicine, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK. christopher.mathew@Genetics.kcl.ac.uk,

    Christopher G. Mathew

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Related links

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DATABASES

OMIM

Crohn disease

type 1 diabetes

FURTHER INFORMATION

dbSNP

ENCODE

HapMap

Wellcome Trust Case Control Consortium

Glossary

Haplotype

The arrangement of the alleles of a series of neighbouring SNPs on the same chromosome.

Ileum

The lower end of the small intestine.

Linkage disequilibrium

A correlation between nearby variants such that the alleles at neighbouring SNPs are non-randomly associated within a population.

Major histocompatibility complex

A highly polymorphic region on chromosome 6 that contains many genes involved in the immune response.

Odds ratio

A measurement of association that is commonly used in case–control studies. It is defined as the odds of exposure to the susceptible genetic variant in cases compared with that in controls. If the odds ratio is significantly greater or less than one, then the genetic variant is associated with the disease.

Tiling microarray

A microarray that carries a set of DNA probes that are complimentary to a series of separate or overlapping DNA sequences across a genomic region. Hybridization of fluorescently labelled cDNA from tissue or cells of interest to the array will detect any transcripts in the genomic regions that are represented by the probes.

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Mathew, C. New links to the pathogenesis of Crohn disease provided by genome-wide association scans. Nat Rev Genet 9, 9–14 (2008). https://doi.org/10.1038/nrg2203

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