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The Genetic Architecture of the Human Immune System: A Bioresource for Autoimmunity and Disease Pathogenesis
Open accessAbstract
Despite recent discoveries of genetic variants associated with autoimmunity and infection, genetic control of the human immune system during homeostasis is poorly understood. We undertook a comprehensive immunophenotyping approach, analyzing 78,000 immune traits in 669 female twins. From the top 151 heritable traits (up to 96% heritable), we used replicated GWAS to obtain 297 SNP associations at 11 genetic loci, explaining up to 36% of the variation of 19 traits. We found multiple associations with canonical traits of all major immune cell subsets and uncovered insights into genetic control for regulatory T cells. This data set also revealed traits associated with loci known to confer autoimmune susceptibility, providing mechanistic hypotheses linking immune traits with the etiology of disease. Our data establish a bioresource that links genetic control elements associated with normal immune traits to common autoimmune and infectious diseases, providing a shortcut to identifying potential mechanisms of immune-related diseases.
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“The heritability for many serum cytokines/chemokines ranges from 50% to 90% in healthy twins between 8 and 82 years of age, with IL-6 and IL-12p40 levels being especially driven by genetics.”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [117]
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“For example, one large-scale GWAS found a median heritability of 37% for a broad set of immune cell types and immune traits, with some phenotypes showing heritability as high as 96% (116, 117).”
From Connecting aging biology and inflammation in the omics era (2022) · cites this paper as [117]
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Metadata
- Authors
- Roederer, M., Quaye, L., Mangino, M., Beddall, M. H., Mahnke, Y., Chattopadhyay, P., Tosi, I., Napolitano, L., Terranova Barberio, M., Menni, C., Villanova, F., Di Meglio, P., Spector, T. D., & Nestle, F. O.
- Affiliations
- National Institutes of Health (US)
- King's College London (GB)
- St Thomas' Hospital (GB)
- Corresponding author
- Roederer, Mario
- Spector, Tim D.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 161
- Issue
- 2
- Pages
- 387-403
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4393780
- OpenAlex
- W2080215939
- Cited by
- 296
- References
- 63
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 27 · 2023: 26 · 2022: 29 · 2021: 27 · 2020: 38 · 2019: 29 · 2018: 31 · 2017: 22 · 2016: 29 · 2015: 10
- FWCI
- 20.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research (NF-SI-0514-10027)
- King's College London
- National Institutes of Health (Z99 AI999999)
- Medical Research Council (MR/J006742/1)
- National Institute of Allergy and Infectious Diseases (ZIAAI005021, ZIAAI005020)
- 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 › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- immune traits, heritability, immune cell subsets, regulatory T cells, autoimmune disease susceptibility, infection susceptibility, genetic loci, single nucleotide polymorphisms, twin studies, immunophenotyping, pathogenesis
- MeSH terms
- Adult, Aged, Autoimmune Diseases, Female, Humans, Immune System Diseases, Leukocytes, Middle Aged, Immunophenotyping, Receptors, IgG, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, T-Lymphocytes, Regulatory, Genome-Wide Association Study
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