Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers
Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2016
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| Online Access: | http://hdl.handle.net/1721.1/100781 https://orcid.org/0000-0002-8017-809X |
| _version_ | 1826202449697832960 |
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| author | Onengut-Gumuscu, Suna Chen, Wei-Min Burren, Oliver Farber, Emily Szpak, Michal Schofield, Ellen Achuthan, Premanand Guo, Hui Stevens, Helen Kundaje, Anshul Kellis, Manolis Deloukas, Panos Wallace, Chris Concannon, Patrick Cooper, Nick J. Quinlan, Aaron R. Mychaleckyj, Josyf C. Bonnie, Jessica K. Fortune, Mary D. Walker, Neil M. Ward, Lucas D. Daly, Mark J. Barrett, Jeffrey C. Cooper, Jason D. Todd, John A. Rich, Stephen S. |
| author2 | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory |
| author_facet | Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Onengut-Gumuscu, Suna Chen, Wei-Min Burren, Oliver Farber, Emily Szpak, Michal Schofield, Ellen Achuthan, Premanand Guo, Hui Stevens, Helen Kundaje, Anshul Kellis, Manolis Deloukas, Panos Wallace, Chris Concannon, Patrick Cooper, Nick J. Quinlan, Aaron R. Mychaleckyj, Josyf C. Bonnie, Jessica K. Fortune, Mary D. Walker, Neil M. Ward, Lucas D. Daly, Mark J. Barrett, Jeffrey C. Cooper, Jason D. Todd, John A. Rich, Stephen S. |
| author_sort | Onengut-Gumuscu, Suna |
| collection | MIT |
| description | Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10[superscript −8]). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34[superscript +] stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal. |
| first_indexed | 2024-09-23T12:07:39Z |
| format | Article |
| id | mit-1721.1/100781 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:07:39Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1007812022-09-28T00:20:21Z Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers Onengut-Gumuscu, Suna Chen, Wei-Min Burren, Oliver Farber, Emily Szpak, Michal Schofield, Ellen Achuthan, Premanand Guo, Hui Stevens, Helen Kundaje, Anshul Kellis, Manolis Deloukas, Panos Wallace, Chris Concannon, Patrick Cooper, Nick J. Quinlan, Aaron R. Mychaleckyj, Josyf C. Bonnie, Jessica K. Fortune, Mary D. Walker, Neil M. Ward, Lucas D. Daly, Mark J. Barrett, Jeffrey C. Cooper, Jason D. Todd, John A. Rich, Stephen S. Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Ward, Lucas D. Kundaje, Anshul Kellis, Manolis Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10[superscript −8]). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34[superscript +] stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal. 2016-01-10T20:56:59Z 2016-01-10T20:56:59Z 2015-03 2014-05 Article http://purl.org/eprint/type/JournalArticle 1061-4036 1546-1718 http://hdl.handle.net/1721.1/100781 Onengut-Gumuscu, Suna, Wei-Min Chen, Oliver Burren, Nick J Cooper, Aaron R Quinlan, Josyf C Mychaleckyj, Emily Farber, et al. “Fine Mapping of Type 1 Diabetes Susceptibility Loci and Evidence for Colocalization of Causal Variants with Lymphoid Gene Enhancers.” Nat Genet 47, no. 4 (March 9, 2015): 381–386. https://orcid.org/0000-0002-8017-809X en_US http://dx.doi.org/10.1038/ng.3245 Nature Genetics Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Nature Publishing Group PMC |
| spellingShingle | Onengut-Gumuscu, Suna Chen, Wei-Min Burren, Oliver Farber, Emily Szpak, Michal Schofield, Ellen Achuthan, Premanand Guo, Hui Stevens, Helen Kundaje, Anshul Kellis, Manolis Deloukas, Panos Wallace, Chris Concannon, Patrick Cooper, Nick J. Quinlan, Aaron R. Mychaleckyj, Josyf C. Bonnie, Jessica K. Fortune, Mary D. Walker, Neil M. Ward, Lucas D. Daly, Mark J. Barrett, Jeffrey C. Cooper, Jason D. Todd, John A. Rich, Stephen S. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers |
| title | Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers |
| title_full | Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers |
| title_fullStr | Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers |
| title_full_unstemmed | Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers |
| title_short | Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers |
| title_sort | fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers |
| url | http://hdl.handle.net/1721.1/100781 https://orcid.org/0000-0002-8017-809X |
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