Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-Regulated Pathway
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Lee, James C; Espeli, Marion; Anderson, Carl A; Linterman, Michelle; Pocock, Joanna M; Williams, Naomi J; Roberts, Rebecca; Viatte, Sebastien; Fu, Bo; Peshu, Norbert; Hien, Tran Tinh; Phu, Nguyen Hoan; Wesley, Emma; Edwards, Cathryn; Ahmad, Tariq; Mansfield, John C; Gearry, Richard; Dunstan, Sarah; Williams, Thomas N; Barton, Anne; Vinuesa, Carola; UK IBD Genetics Consortium; Parkes, Miles; Lyons, Paul A; Smith, Kenneth G C
Description
The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease...[Show more]
dc.contributor.author | Lee, James C | |
---|---|---|
dc.contributor.author | Espeli, Marion | |
dc.contributor.author | Anderson, Carl A | |
dc.contributor.author | Linterman, Michelle | |
dc.contributor.author | Pocock, Joanna M | |
dc.contributor.author | Williams, Naomi J | |
dc.contributor.author | Roberts, Rebecca | |
dc.contributor.author | Viatte, Sebastien | |
dc.contributor.author | Fu, Bo | |
dc.contributor.author | Peshu, Norbert | |
dc.contributor.author | Hien, Tran Tinh | |
dc.contributor.author | Phu, Nguyen Hoan | |
dc.contributor.author | Wesley, Emma | |
dc.contributor.author | Edwards, Cathryn | |
dc.contributor.author | Ahmad, Tariq | |
dc.contributor.author | Mansfield, John C | |
dc.contributor.author | Gearry, Richard | |
dc.contributor.author | Dunstan, Sarah | |
dc.contributor.author | Williams, Thomas N | |
dc.contributor.author | Barton, Anne | |
dc.contributor.author | Vinuesa, Carola | |
dc.contributor.author | UK IBD Genetics Consortium | |
dc.contributor.author | Parkes, Miles | |
dc.contributor.author | Lyons, Paul A | |
dc.contributor.author | Smith, Kenneth G C | |
dc.date.accessioned | 2014-02-18T03:48:46Z | |
dc.date.available | 2014-02-18T03:48:46Z | |
dc.identifier.issn | 0092-8674 | |
dc.identifier.uri | http://hdl.handle.net/1885/11391 | |
dc.description.abstract | The clinical course and eventual outcome, or prognosis, of complex diseases varies enormously between affected individuals. This variability critically determines the impact a disease has on a patient’s life but is very poorly understood. Here, we exploit existing genome-wide association study data to gain insight into the role of genetics in prognosis. We identify a noncoding polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite not being associated with disease susceptibility, is associated with a milder course of Crohn’s disease and rheumatoid arthritis and with increased risk of severe malaria. Minor allele carriage is shown to limit inflammatory responses in monocytes via a FOXO3-driven pathway, which through TGFb1 reduces production of proinflammatory cytokines, including TNFa, and increases production of anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic contribution to prognosis in distinct diseases that operates via a FOXO3-driven pathway modulating inflammatory responses. | |
dc.format | 13 pages | |
dc.publisher | Elsevier | |
dc.rights | This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. | |
dc.source | Cell 155 (2013): 57-69 | |
dc.subject | human SNP | |
dc.subject | inflammatory | |
dc.subject | infectious disease | |
dc.title | Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-Regulated Pathway | |
dc.type | Journal article | |
local.identifier.citationvolume | 155 | |
dcterms.dateAccepted | 2013-08-19 | |
dc.date.issued | 2013-09-26 | |
local.identifier.absfor | 110309 - Infectious Diseases | |
local.identifier.ariespublication | f5625xPUB4382 | |
local.publisher.url | http://www.cell.com/cellpress | |
local.type.status | Published Version | |
local.contributor.affiliation | Williams, Naomi J, Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University | |
local.contributor.affiliation | Vinuesa, Carola G, Department of Pathogens and Immunity, John Curtin School of Medical Research, Australian National University | |
local.bibliographicCitation.issue | 1 | |
local.bibliographicCitation.startpage | 57 | |
local.bibliographicCitation.lastpage | 69 | |
local.identifier.doi | 10.1037/a0032650 | |
dc.date.updated | 2015-12-11T08:55:15Z | |
local.identifier.scopusID | 2-s2.0-84884851276 | |
local.identifier.thomsonID | 000324916700009 | |
Collections | ANU Research Publications |
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