Cell-specific protein phenotypes for the autoimmune locus IL2RA using a genotype-selectable human bioresource
Open accessAbstract
Genome-wide association studies (GWAS) have identified over 300 regions associated with more than 70 common diseases. However, identifying causal genes within an associated region remains a major challenge. One approach to resolving causal genes is through the dissection of gene-phenotype correlations. Here we use polychromatic flow cytometry to show that differences in surface expression of the human interleukin-2 (IL-2) receptor alpha (IL2RA, or CD25) protein are restricted to particular immune cell types and correlate with several haplotypes in the IL2RA region that have previously been associated with two autoimmune diseases, type 1 diabetes (T1D) and multiple sclerosis. We confirm our strongest gene-phenotype correlation at the RNA level by allele-specific expression (ASE). We also define key parameters for the design and implementation of post-GWAS gene-phenotype investigations and demonstrate the usefulness of a large bioresource of genotype-selectable normal donors from whom fresh, primary cells can be analyzed.
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T-cell surface expression of IL-12 receptor alpha (CD25) is associated with risk variants for both MS and type 1 diabetes.
“T‐cell surface expression of IL‐12 receptor alpha (CD25) is associated with risk variants for both MS and type 1 diabetes.72”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [72]
The paper’s main text reports that IL2RA risk-related haplotypes correlate with surface CD25 expression on CD4+ T-cell subsets, and discusses phenotypes implicated in both type 1 diabetes and multiple sclerosis. But the claim misidentifies CD25 as IL-12 receptor alpha; the paper identifies it as IL-2 receptor alpha (IL2RA). Our copy provides no page number for these passages. (LLM, conf=0.90)
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- Authors
- Dendrou, C. A., Plagnol, V., Fung, E., Yang, J. H. M., Downes, K., Cooper, J. D., Nutland, S., Coleman, G., Himsworth, M., Hardy, M., Burren, O., Healy, B., Walker, N. M., Koch, K., Ouwehand, W. H., Bradley, J. R., Wareham, N. J., Todd, J. A., & Wicker, L. S.
- Affiliations
- University of Cambridge (GB)
- NHS Blood and Transplant (GB)
- Addenbrooke's Hospital (GB)
- Corresponding author
- Wicker, Linda S
- ORCID
- Venue
- Nature Genetics
- Published
- 2009-08-23
- Volume
- 41
- Issue
- 9
- Pages
- 1011-1015
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2749506
- OpenAlex
- W2080664482
- Cited by
- 274
- References
- 31
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 10 · 2023: 2 · 2022: 8 · 2021: 6 · 2020: 6 · 2019: 13 · 2018: 11 · 2017: 16 · 2016: 12 · 2015: 30 · 2014: 18 · 2013: 35 · 2012: 30
- FWCI
- 19.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (061859, 061858, 079895)
- National Institute for Health and Care Research (NF-SI-0508-10275)
- National Institute of Allergy and Infectious Diseases (P01AI39671, P01AI039671)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL2RA, CD25, IL-2 receptor alpha, single nucleotide polymorphisms, type 1 diabetes, multiple sclerosis, autoimmune disease, haplotypes, gene-phenotype correlation, allele-specific expression, primary immune cells, causal gene identification
- MeSH terms
- Adolescent, Adult, Alleles, Chromosomes, Human, Pair 10, Diabetes Mellitus, Type 1, Female, Gene Frequency, Genotype, Haplotypes, Heterozygote, Homozygote, Humans, Immunologic Memory, Male, Middle Aged, Multiple Sclerosis, Phenotype, T-Lymphocytes, CD4-Positive T-Lymphocytes, Case-Control Studies, Biological Specimen Banks, Quantitative Trait, Heritable, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, T-Lymphocytes, Regulatory, Interleukin-2 Receptor alpha Subunit, Genome-Wide Association Study, Young Adult
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