Immune-mediated disease genetics: the shared basis of pathogenesis
Abstract
Recent genetic studies in multiple autoimmune and inflammatory diseases have identified hundreds of genomic loci harboring risk variants. These variants are shared between diseases at unexpectedly high rates, providing a molecular basis for the shared pathogenesis of immune-mediated disease. If properly used, these results could allow us to identify specific pathways underlying disease; explain disease heterogeneity by grouping patients by molecular causes rather than overall symptomatology; and develop more rational approaches to diagnosis and therapy targeting these molecular defects. Here we review the current state of play in the genetics of immune-mediated disease, evidence for this sharing and how this new knowledge can lead to medically actionable discoveries of pathobiology.
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Perturbations to key immune processes mediate risk to multiple diseases.
“These results suggest that perturbations to key immune processes mediate risk to multiple diseases.”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [69]
Associations unique to MS may identify disease-specific biology, including CNS-relevant mechanisms.
“those associations unique to MS may identify disease‐specific biology, including CNS‐relevant mechanisms.69”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [69]
Many loci were associated with multiple diseases and the genes encoded in those loci fall into distinct immune pathways.
“many loci were associated with multiple diseases and that the genes encoded in those loci fall into distinct immune pathways.69, 70”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [69]
Cites
Finding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336 · see citing works
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821 · see citing works
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013 · see citing works
Genome-wide association studies for complex traits: consensus, uncertainty and challenges
McCarthy, M. I., Abecasis, G. R., Cardon, L. R., Goldstein, D. B., Little, J., Ioannidis, J. P. A., & Hirschhorn, J. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2344 · Cited by 2,891 · see citing works
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
The International Multiple Sclerosis Genetics Consortium & The Wellcome Trust Case Control Consortium 2 (2011) · Nature · doi:10.1038/nature10251 · Cited by 2,697 · see citing works
Heritability in the genomics era — concepts and misconceptions
Visscher, P. M., Hill, W. G., & Wray, N. R. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2322 · Cited by 1,921 · see citing works
Patterns and rates of exonic de novo mutations in autism spectrum disorders
Neale, B. M., Kou, Y., Liu, L., Ma’ayan, A., Samocha, K. E., Sabo, A., Lin, C.-F., Stevens, C., Wang, L.-S., Makarov, V., et al. (2012) · Nature · doi:10.1038/nature11011 · Cited by 1,734 · see citing works
Nejentsev, S., Walker, N., Riches, D., Egholm, M., & Todd, J. A. (2009) · Science · doi:10.1126/science.1167728 · Cited by 958 · see citing works
The genetics and immunopathogenesis of inflammatory bowel disease
Cho, J. H. (2008) · Nature Reviews Immunology · doi:10.1038/nri2340 · Cited by 940 · see citing works
Pervasive Sharing of Genetic Effects in Autoimmune Disease
Cotsapas, C., Voight, B. F., Rossin, E., Lage, K., Neale, B. M., Wallace, C., Abecasis, G. R., Barrett, J. C., Behrens, T., Cho, J., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002254 · Cited by 606 · see citing works
Self-citationDendrou, C. A., Plagnol, V., Fung, E., Yang, J. H. M., Downes, K., Cooper, J. D., Nutland, S., Coleman, G., Himsworth, M., Hardy, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.434 · Cited by 274 · see citing works
Synthetic Associations Created by Rare Variants Do Not Explain Most GWAS Results
Wray, N. R., Purcell, S. M., & Visscher, P. M. (2011) · PLoS Biology · doi:10.1371/journal.pbio.1000579 · Cited by 176 · see citing works
Guilt beyond a reasonable doubt
Altshuler, D., & Daly, M. (2007) · Nature Genetics · doi:10.1038/ng0707-813 · Cited by 151 · see citing works
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Roederer, M., Quaye, L., Mangino, M., Beddall, M. H., Mahnke, Y., Chattopadhyay, P., Tosi, I., Napolitano, L., Terranova Barberio, M., Menni, C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.02.046 · Cited by 296 · see citing works
Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis
Li, K., Wei, S., Hu, L., Yin, X., Mai, Y., Jiang, C., Peng, X., Cao, X., Huang, Z., Zhou, H., et al. (2020) · Mediators of Inflammation · doi:10.1155/2020/2058272 · Cited by 92 · see citing works
Genome‐wide association studies of multiple sclerosis
Cotsapas, C., & Mitrovic, M. (2018) · Clinical & Translational Immunology · doi:10.1002/cti2.1018 · Cited by 89 · see citing works
Self-citationLiang, J., Hänsch, G. M., Hübner, K., & Samstag, Y. (2019) · Advances in Biological Regulation · doi:10.1016/j.jbior.2018.11.006 · Cited by 72 · see citing works
Multiple sclerosis-associated CLEC16A controls HLA class II expression via late endosome biogenesis
van Luijn, M. M., Kreft, K. L., Jongsma, M. L., Mes, S. W., Wierenga-Wolf, A. F., van Meurs, M., Melief, M.-J., der Kant, R. V., Janssen, L., Janssen, H., et al. (2015) · Brain · doi:10.1093/brain/awv080 · Cited by 68 · see citing works
- Authors
- Cotsapas, C., & Hafler, D. A.
- Affiliations
- Yale University (US)
- Corresponding author
- Cotsapas, Chris
- Venue
- Trends in Immunology
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 34
- Issue
- 1
- Pages
- 22-26
- ISSN
- 1471-4906 (ISSN-L)
- OpenAlex
- W2078169669
- Cited by
- 109
- References
- 13
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 8 · 2020: 13 · 2019: 10 · 2018: 10 · 2017: 8 · 2016: 9 · 2015: 21 · 2014: 2 · 2013: 6 · 2012: 1
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- immune-mediated diseases, autoimmune disease, inflammatory diseases, shared genetic risk loci, pathogenesis, genetic heterogeneity, disease classification, therapeutic target, pathobiology
- MeSH terms
- Genetic Testing, Humans, Immune System, Risk Factors, Genetic Predisposition to Disease, Genome-Wide Association Study
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