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

Parkes, M., Cortes, A., Van Heel, D. A., & Brown, M. A. (2013) Genetic insights into common pathways and complex relationships among iImmune-mediated diseases. Nature Reviews Genetics, 14(9), pp. 661-673.

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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. © 2013 Macmillan Publishers Limited. All rights reserved.

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ID Code: 89281
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :77
Export Date: 21 September 2015
CODEN: NRGAA
Correspondence Address: Parkes, M.; Inflammatory Bowel Disease Research Group, Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom; email: mp372@cam.ac.uk
Keywords: HLA antigen class 2, I kappa B, interferon regulatory factor, interleukin 23, allele, ankylosing spondylitis, autoimmune disease, bioinformatics, celiac disease, Crohn disease, effect size, enteritis, environmental exposure, ethnicity, gene frequency, gene linkage disequilibrium, gene locus, genetic association, genetic susceptibility, genotype, heritability, HLA system, insulin dependent diabetes mellitus, lymphocyte activation, multiple sclerosis, priority journal, psoriasis, review, rheumatoid arthritis, single nucleotide polymorphism, systemic lupus erythematosus, Alleles, Animals, Chromosome Mapping, Environment, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Immune System Diseases, Quantitative Trait Loci, Signal Transduction
DOI: 10.1038/nrg3502
ISSN: 1471-0056
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: © 2013 Macmillan Publishers Limited
Deposited On: 20 Oct 2015 00:24
Last Modified: 19 Feb 2016 04:25

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