Genetic Mechanisms Highlight Shared Pathways for the Pathogenesis of Polygenic Type 1 Diabetes and Monogenic Autoimmune Diabetes
dc.contributor.author | Johnson, MB | |
dc.contributor.author | Cerosaletti, K | |
dc.contributor.author | Flanagan, SE | |
dc.contributor.author | Buckner, JH | |
dc.date.accessioned | 2019-04-02T14:10:01Z | |
dc.date.issued | 2019-03-19 | |
dc.description.abstract | PURPOSE OF REVIEW: To highlight pathways important for the development of autoimmune diabetes by investigating shared mechanisms of disease in polygenic and monogenic diabetes. RECENT FINDINGS: Genome-wide association studies have identified 57 genetic risk loci for type 1 diabetes. Progress has been made in unravelling the mechanistic effects of some of these variants, providing key insights into the pathogenesis of type 1 diabetes. Seven monogenic disorders have also been described where diabetes features as part of an autoimmune syndrome. Studying these genes in relation to polygenic risk loci provides a unique opportunity to dissect pathways important for the development of immune-mediated diabetes. Monogenic autoimmune diabetes can result from the dysregulation of multiple pathways suggesting that small effects on many immune processes are required to drive the autoimmune attack on pancreatic beta cells in polygenic type 1 diabetes. A breakdown in central and peripheral immune tolerance is a common theme in the genetic mechanisms of both monogenic and polygenic disease which highlights the importance of these checkpoints in the development and treatment of islet autoimmunity. | en_GB |
dc.description.sponsorship | National Institutes of Health (NIH) | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Royal Society | en_GB |
dc.identifier.citation | Vol. 19, article 20 | en_GB |
dc.identifier.doi | 10.1007/s11892-019-1141-6 | |
dc.identifier.grantnumber | 1DP3DK111802 | en_GB |
dc.identifier.grantnumber | 105636/Z/14/Z | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/36708 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/30888520 | en_GB |
dc.rights | © The Author(s) 2019. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. | en_GB |
dc.subject | Autoimmunity | en_GB |
dc.subject | Immune tolerance | en_GB |
dc.subject | Monogenic diabetes | en_GB |
dc.subject | Polygenic risk | en_GB |
dc.title | Genetic Mechanisms Highlight Shared Pathways for the Pathogenesis of Polygenic Type 1 Diabetes and Monogenic Autoimmune Diabetes | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-04-02T14:10:01Z | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the final version. Available on open access from Springer via the DOI in this record | en_GB |
dc.identifier.eissn | 1539-0829 | |
dc.identifier.journal | Current Diabetes Reports | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-03-19 | |
exeter.funder | ::Wellcome Trust | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-03-19 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-04-02T14:07:26Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2019-04-02T14:10:04Z | |
refterms.panel | A | en_GB |
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This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.