Journal article
Human SNP links differential outcomes in inflammatory and infectious disease to a FOXO3-regulated pathway
JC Lee, M Espéli, CA Anderson, MA Linterman, JM Pocock, NJ Williams, R Roberts, S Viatte, B Fu, N Peshu, TT Hien, NH Phu, E Wesley, C Edwards, T Ahmad, JC Mansfield, R Gearry, S Dunstan, TN Williams, A Barton Show all
Cell | CELL PRESS | Published : 2013
Abstract
Summary 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 respo..
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Awarded by Wellcome Trust
Funding Acknowledgements
We gratefully thank the following: Cambridge BioResource (CBR) volunteers, the CBR staff for coordinating volunteer recruitment, and the CBR SAB for support; Emma Whitelaw (QIMR) for providing Foxo3a<SUP>MommeR1</SUP> mice; Prof Adam Young (PI-NOAR) and Prof Deborah Symons (PI-ERAS) for collaboration; Alex W. Macharia, Sophie Uyoga, Carolyne Ndila, Emily Nyatichi, Metrine Tendwa, Johnstone Mkale, Adan Mohamed, Prophet Ingosi, and Mary Njoroge for DNA extraction at the KEMRI-Wellcome Trust Programme; and Gideon Nyutu, Kenneth Magua, and Ruth Mwarabu for database support. This work is published with permission from the director of KEMRI, supported by NIHR Biomedical Research centers in Cambridge and Manchester, and funded by the Wellcome Trust (program grant 083650/Z/07/Z, grants to J.C.L. 087007/Z/08/Z, C.A.A. 098051 and T.N.W. 091758/Z/10/Z), Arthritis Research UK and the Swiss Foundation for Medical Science (grant to S.V. PASMP3_134380). The Cambridge Institute for Medical Research is in receipt of Wellcome Trust Strategic Award (079895).