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A rare IL2RA haplotype identifies SNP rs61839660 as causal for autoimmunity
View ORCID ProfileDaniel B. Rainbow, View ORCID ProfileMarcin Pekalski, View ORCID ProfileAntony J. Cutler, View ORCID ProfileOliver Burren, View ORCID ProfileNeil Walker, View ORCID ProfileJohn A. Todd, View ORCID ProfileChris Wallace, View ORCID ProfileLinda S. Wicker
doi: https://doi.org/10.1101/108126
Daniel B. Rainbow
1JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
2JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust/MRC Building, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Research Campus, Cambridge, UK.
Marcin Pekalski
1JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
2JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust/MRC Building, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Research Campus, Cambridge, UK.
Antony J. Cutler
1JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
2JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust/MRC Building, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Research Campus, Cambridge, UK.
Oliver Burren
2JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust/MRC Building, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Research Campus, Cambridge, UK.
3Department of Medicine, Box 157, Level 4, Cambridge Biomedical Campus, University of Cambridge, UK.
Neil Walker
2JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust/MRC Building, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Research Campus, Cambridge, UK.
4Current address Clinical Informatics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
John A. Todd
1JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
2JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust/MRC Building, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Research Campus, Cambridge, UK.
Chris Wallace
3Department of Medicine, Box 157, Level 4, Cambridge Biomedical Campus, University of Cambridge, UK.
5MRC Biostatistics Unit, University of Cambridge, School of Clinical Medicine, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge, UK.
Linda S. Wicker
1JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
2JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Wellcome Trust/MRC Building, Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Research Campus, Cambridge, UK.
Abstract
IL2RA is associated with multiple autoimmune diseases including type 1 diabetes (T1D). Higher expression of IL2RA mRNA and its protein product CD25 in T lymphocytes is associated with a T1D-protective haplotype. Here we show that a rare variation of this haplotype that loses the protective allele at a single SNP, rs61839660, reduces IL2RA expression and T1D protection, identifying it as the causal factor in disease.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Posted February 14, 2017.
A rare IL2RA haplotype identifies SNP rs61839660 as causal for autoimmunity
Daniel B. Rainbow, Marcin Pekalski, Antony J. Cutler, Oliver Burren, Neil Walker, John A. Todd, Chris Wallace, Linda S. Wicker
bioRxiv 108126; doi: https://doi.org/10.1101/108126
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