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Class II HLA interactions modulate genetic risk for multiple sclerosis


Moutsianas, L and Jostins, L and Beecham, AH and Dilthey, AT and Xifara, DK and Ban, M and Shah, TS and Patsopoulos, NA and Alfredsson, L and Anderson, CA and Attfield, KE and Baranzini, SE and Barrett, J and Binder, TMC and Booth, D and Buck, D and Celius, EG and Cotsapas, C and D'Alfonso, S and Dendrou, CA and Donnelly, P and Dubois, B and Fontaine, B and Fugger, L and Goris, A and Gourraud, P-A and Graetz, C and Hemmer, B and Hillert, J and Kockum, I and Leslie, S and Lill, CM and Martinelli-Boneschi, F and Oksenberg, JR and Olsson, T and Oturai, A and Saarela, J and Sondergaard, HB and Spurkland, A and Taylor, B and Winkelmann, J and Zipp, F and Haines, JL and Pericak-Vance, MA and Spencer, CCA and Stewart, G and Hafler, DA and Ivinson, AJ and Harbo, HF and Hauser, SL and De Jager, PL and Compston, A and McCauley, JL and Sawcer, S and McVean, G, for the International Multiple Sclerosis Genetics Consortium, Class II HLA interactions modulate genetic risk for multiple sclerosis, Nature Genetics, 47, (10) pp. 1107-1113. ISSN 1061-4036 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 Nature America

DOI: doi:10.1038/ng.3395


Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01-HLA-DRB1*15:01 and HLA-DQB1*03:01-HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Taylor, B (Professor Bruce Taylor)
ID Code:103390
Year Published:2015
Web of Science® Times Cited:212
Deposited By:Menzies Institute for Medical Research
Deposited On:2015-10-07
Last Modified:2017-11-06

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