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Nat Rev Genet. 2013 Sep;14(9):661-73. doi: 10.1038/nrg3502. Epub 2013 Aug 6.

Genetic insights into common pathways and complex relationships among immune-mediated diseases.

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1
1] Inflammatory Bowel Disease Research Group, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK. [2].

Abstract

Shared aetiopathogenic factors among immune-mediated diseases have long been suggested by their co-familiality and co-occurrence, and molecular support has been provided by analysis of human leukocyte antigen (HLA) haplotypes and genome-wide association studies. The interrelationships can now be better appreciated following the genotyping of large immune disease sample sets on a shared SNP array: the 'Immunochip'. Here, we systematically analyse loci shared among major immune-mediated diseases. This reveals that several diseases share multiple susceptibility loci, but there are many nuances. The most associated variant at a given locus frequently differs and, even when shared, the same allele often has opposite associations. Interestingly, risk alleles conferring the largest effect sizes are usually disease-specific. These factors help to explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap.

PMID:
23917628
DOI:
10.1038/nrg3502
[Indexed for MEDLINE]
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