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Immunogenetics of systemic sclerosis: Defining heritability, functional variants and shared-autoimmunity pathways
Lara Bossini-Castillo1, Elena López-Isac1, Javier Martín1
1Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas (IPBLN-CSIC), Parque Tecnológico de La Salud (PTS), Granada, Spain.
Journal of Autoimmunity
|July 28, 2015
Summary
Genomic studies reveal significant genetic factors influencing Systemic Sclerosis (SSc), a complex autoimmune disease. Our findings indicate a stronger genetic contribution to SSc than previously understood, paving the way for new treatments.
Area of Science:
- Immunogenetics
- Rheumatology
- Computational Biology
Background:
- Systemic Sclerosis (SSc) is a heterogeneous autoimmune connective tissue disease with complex genetic underpinnings.
- Previous genetic studies, including genome-wide association studies (GWASs), have identified numerous SSc risk loci.
- The heritability of SSc has been debated, with twin studies suggesting low estimates.
Purpose of the Study:
- To provide an updated overview of genetic factors associated with Systemic Sclerosis.
- To analyze the role of these genetic factors in SSc pathogenesis, including immune response, apoptosis, autophagy, and fibrosis.
- To re-evaluate SSc heritability using GWAS data and explore genetic overlap with other autoimmune diseases.
Main Methods:
- Review of recent findings from large-scale genetic studies (GWASs, Immunochip).
- Classification of 18 non-HLA risk factors based on their involvement in immune response, apoptosis, autophagy, or fibrosis.
- Recalculation of narrow-sense SSc heritability using GWAS data.
- Functional annotation of SSc-associated single nucleotide polymorphisms (SNPs) and their proxies.
- Analysis of genetic overlap between SSc and other autoimmune diseases (ADs).
Main Results:
- Identified and classified 18 non-HLA risk factors involved in key pathogenic pathways of SSc.
- Recalculated heritability estimates suggest a greater genetic influence on SSc than previously reported.
- Significant genetic overlap exists between SSc and other autoimmune diseases, particularly systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis.
Conclusions:
- Genetics plays a more substantial role in Systemic Sclerosis than previously estimated.
- Understanding the function of SSc-associated genetic variants can elucidate disease mechanisms.
- The shared genetic architecture with other autoimmune diseases offers insights into common pathogenic pathways and potential therapeutic targets.
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