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Autoimmune diseases: insights from genome-wide association studies

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Lettre, G., Rioux, J. D.·2008·Human Molecular Genetics
DOI 10.1093/hmg/ddn246PMC PMC2782355
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Abstract

Autoimmune diseases occur when an individual's own immune system attacks and destroys his or her healthy cells and tissues. Although it is clear that environmental stimuli can predispose someone to develop autoimmune diseases, twin- and family-based studies have shown that genetic factors also play an important role in modifying disease risk. Because many of these diseases are relatively common (prevalence in European-derived populations: 0.01-1%) and exhibit a complex mode of inheritance, many DNA sequence variants with modest effect on disease risk contribute to the genetic burden. Recently, the completion of the HapMap project, together with the development of new genotyping technologies, has given human geneticists the tools necessary to comprehensively, and in an unbiased manner, search our genome for DNA polymorphisms associated with many autoimmune diseases. Here we review recent progress made in the identification of genetic risk factors for celiac disease, Crohn's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and type-1 diabetes using genome-wide association studies (GWAS). Strikingly, GWAS have increased the number of genetic risk variants associated with these autoimmune diseases from 15 before 2006 to 68 now. We summarize what this new genetic landscape teaches us in terms of the pathogenesis of these diseases, and highlight some of the outstanding challenges ahead. Finally, we open a discussion on ways to best maximize the impact of these genetic discoveries where it matters the most, that is for autoimmune disease patients.

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  • These results suggest that overall genetic correlations may obscure a more complex set of genetic relationships at the level of specific loci and pathways.

    “These results underscore the complexity of genetic relationships among related disorders and suggest that overall genetic correlations may obscure a more complex set of genetic relationships at the level of specific loci and pathways, as seen in immune-mediated diseases (Baurecht et al., 2015; Lettre and Rioux, 2008; Schmitt et al., 2016).”

    From Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders (2019) · cites this paper as Lettre and Rioux, 2008

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Cited by

Sorted by citations

Authors
Lettre, G., & Rioux, J. D.
Affiliations
  • Broad Institute (US)
  • Montreal Heart Institute (CA)
Corresponding author
Rioux, J. D.
ORCID
Venue
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Published
2008-10-15
Volume
17
Issue
R2
Pages
R116-R121
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
DOI
10.1093/hmg/ddn246
PMC
PMC2782355
OpenAlex
W2120388891
Cited by
317
References
5
Citations by year
2026: 2 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 14 · 2021: 15 · 2020: 13 · 2019: 14 · 2018: 12 · 2017: 12 · 2016: 11 · 2015: 16 · 2014: 13 · 2013: 14 · 2012: 26
FWCI
4.12
Type
journal article
Language
en
Open access
Locations
  • Human Molecular Genetics (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (P01AI065687, U19AI067152, AI065687, AI-067152)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK064869, DK062432, R01DK064869, U01DK062432)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
autoimmune disease, genetic risk factors, genome-wide association study, celiac disease, Crohn's disease, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, DNA sequence variants, pathogenesis, HapMap, genotyping technologies
MeSH terms
Arthritis, Rheumatoid, Autoimmune Diseases, Crohn Disease, Diabetes Mellitus, Type 1, Humans, Lupus Erythematosus, Systemic, Multiple Sclerosis, Risk Factors, Genetic Predisposition to Disease, Genome-Wide Association Study

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