Context-specific effects of genetic variants associated with autoimmune disease

Research output: Contribution to journalReview articleAcademicpeer-review

22 Citations (Scopus)
271 Downloads (Pure)


Autoimmune diseases such as rheumatoid arthritis and coeliac disease are typical examples of complex genetic diseases caused by a combination of genetic and non-genetic risk factors. Insight into the genetic risk factors (single nucleotide polymorphisms (SNPs)) has increased since genome-wide association studies (GWAS) became possible in 2007 and, for individual diseases, SNPs can now explain some 15-50% of genetic risk. GWAS have also shown that some 50% of the genetic risk factors for individual autoimmune diseases overlap between different diseases. Thus, shared risk factors may converge to pathways that, when perturbed by genetic variation, predispose to autoimmunity in general. This raises the question of what determines disease specificity, and suggests that identical risk factors may have different effects in various autoimmune diseases. Addressing this question requires translation of genetic risk factors to causal genes and then to molecular and cellular pathways. Since > 90% of the genetic risk factors are found in the non-coding part of the genome (i.e. outside the exons of protein-coding genes) and can have an impact on gene regulation, there is an urgent need to better understand the non-coding part of the genome. Here, we will outline the methods being used to unravel the gene regulatory networks perturbed in autoimmune diseases and the importance of doing this in the relevant cell types. We will highlight findings in coeliac disease, which manifests in the small intestine, to demonstrate how cell type and disease context can impact on the consequences of genetic risk factors.

Original languageEnglish
Pages (from-to)R185-R192
Number of pages8
JournalHuman Molecular Genetics
Issue numberR2
Publication statusPublished - 1-Oct-2017


  • Arthritis, Rheumatoid/genetics
  • Autoimmune Diseases/etiology
  • Autoimmunity/genetics
  • Gene Expression Regulation/genetics
  • Gene Regulatory Networks/genetics
  • Genetic Predisposition to Disease
  • Genetic Variation/genetics
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide/genetics
  • Quantitative Trait Loci
  • Risk Factors

Cite this