Context-specific effects of genetic variants associated with autoimmune disease
| Autor: | Cisca Wijmenga, Iris Jonkers |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genotype Quantitative Trait Loci Genome-wide association study Single-nucleotide polymorphism Autoimmunity Disease Autoimmune Diseases/etiology Biology Polymorphism Single Nucleotide Gene Expression Regulation/genetics Autoimmune Diseases Arthritis Rheumatoid 03 medical and health sciences Risk Factors Genetic variation Genetics medicine Humans Invited Reviews Gene Regulatory Networks Genetic Predisposition to Disease Polymorphism Molecular Biology Genetics (clinical) Genetic association Autoimmune disease Arthritis Genetic Variation Rheumatoid/genetics General Medicine medicine.disease 3. Good health 030104 developmental biology Gene Expression Regulation Genetic Variation/genetics Autoimmunity/genetics Single Nucleotide/genetics Common disease-common variant Gene Regulatory Networks/genetics Genome-Wide Association Study |
| Zdroj: | Human Molecular Genetics |
| ISSN: | 0964-6906 |
| DOI: | 10.1093/hmg/ddx254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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