Unravelling the Shared Genetic Mechanisms Underlying 18 Autoimmune Diseases Using a Systems Approach
Open accessPublished version of a preprint
Abstract
Autoimmune diseases (AiDs) are complex heterogeneous diseases characterized by hyperactive immune responses against self. Genome-wide association studies have identified thousands of single nucleotide polymorphisms (SNPs) associated with several AiDs. While these studies have identified a handful of pleiotropic loci that confer risk to multiple AiDs, they lack the power to detect shared genetic factors residing outside of these loci. Here, we integrated chromatin contact, expression quantitative trait loci and protein-protein interaction (PPI) data to identify genes that are regulated by both pleiotropic and non-pleiotropic SNPs. The PPI analysis revealed complex interactions between the shared and disease-specific genes. Furthermore, pathway enrichment analysis demonstrated that the shared genes co-occur with disease-specific genes within the same biological pathways. In conclusion, our results are consistent with the hypothesis that genetic risk loci associated with multiple AiDs converge on a core set of biological processes that potentially contribute to the emergence of polyautoimmunity.
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Cites
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- Authors
- Gokuladhas, S., Schierding, W., Golovina, E., Fadason, T., & O’Sullivan, J.
- Affiliations
- University of Auckland (NZ)
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2021-08-13
- Volume
- 12
- Pages
- 693142-693142
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC8415031
- OpenAlex
- W3195527362
- Cited by
- 25
- References
- 3
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 3 · 2022: 9 · 2021: 1
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Royal Society Te Apārangi (16-UOO-072)
- Auckland Medical Research Foundation (ID 1320002, 1320002)
- Ministry of Business, Innovation and Employment (UOAX1611)
- National Institutes of Health
- Marsden Fund (16-UOO-072)
- National Heart, Lung, and Blood Institute
- National Institute of Mental Health
- National Institute on Drug Abuse
- National Human Genome Research Institute
- NIH Office of the Director
- National Cancer Institute
- National Institute of Neurological Disorders and Stroke
- Common Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- autoimmune disease, shared genetic mechanisms, polyautoimmunity, pleiotropic loci, chromatin interactions, expression quantitative trait loci, protein-protein interaction, pathway enrichment, disease risk loci, systems genetics
- MeSH terms
- Autoimmune Diseases, Humans, Phenotype, Autoimmunity, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genomics, Databases, Genetic, Quantitative Trait Loci, Systems Biology, Gene Regulatory Networks, Protein Interaction Maps
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