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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles
  • Animals
  • Chromosome Mapping
  • Environment
  • Gene-Environment Interaction
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Immune System Diseases / genetics*
  • Immune System Diseases / metabolism*
  • Quantitative Trait Loci*
  • Signal Transduction*