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

Parkes, Miles, Cortes, Adrian, van Heel, David A. and Brown, Matthew A. (2013) Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nature Reviews Genetics, 14 9: 661-673. doi:10.1038/nrg3502


Author Parkes, Miles
Cortes, Adrian
van Heel, David A.
Brown, Matthew A.
Title Genetic insights into common pathways and complex relationships among immune-mediated diseases
Journal name Nature Reviews Genetics   Check publisher's open access policy
ISSN 1471-0056
1471-0064
Publication date 2013-09-01
Year available 2013
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1038/nrg3502
Open Access Status DOI
Volume 14
Issue 9
Start page 661
End page 673
Total pages 13
Place of publication London United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1312 Molecular Biology
1311 Genetics
2716 Genetics (clinical)
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.
Formatted 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.
Keyword Genome-Wide Association
Inflammatory-Bowel-Disease
Seropositive Rheumatoid-Arthritis
Psoriasis Susceptibility Loci
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
 
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