Class II HLA interactions modulate genetic risk for multiple sclerosis

L Moutsianas; L Jostins; AH Beecham; AT Dilthey; DK Xifara; M Ban; TS Shah; NA Patsopoulos; L Alfredsson; CA Anderson; KE Attfield; SE Baranzini; J Barrett; TMC Binder; D Booth; D Buck; EG Celius; C Cotsapas; S D'Alfonso; CA Dendrou; P Donnelly; B Dubois; B Fontaine; L Fugger; A Goris; PA Gourraud; C Graetz; B Hemmer; J Hillert; I Kockum; S Leslie; CM Lill; F Martinelli-Boneschi; JR Oksenberg; T Olsson; A Oturai; J Saarela; HB SØndergaard; A Spurkland; B Taylor; J Winkelmann; F Zipp; J L Haines; MA Pericak-Vance; CCA Spencer; G Stewart; DA Hafler; AJ Ivinson; HF Harbo; SL Hauser; PL De Jager; A Compston; JL McCauley; S Sawcer; G McVean

Journal article

Class II HLA interactions modulate genetic risk for multiple sclerosis

L Moutsianas, L Jostins, AH Beecham, AT Dilthey, DK Xifara, M Ban, TS Shah, NA Patsopoulos, L Alfredsson, CA Anderson, KE Attfield, SE Baranzini, J Barrett, TMC Binder, D Booth, D Buck, EG Celius, C Cotsapas, S D'Alfonso, CA Dendrou Show all

Nature Genetics | NATURE PUBLISHING GROUP | Published : 2015

DOI: 10.1038/ng.3395

Abstract

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 clas..

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University of Melbourne Researchers

Stephen Leslie Author

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Grants

Awarded by Gemeinnützige Hertie-Stiftung

Funding Acknowledgements

We thank the individuals, nurses and referring physicians who participated in this study. This project was supported by the US National Institutes of Health (NS049477, NS26799, R01NS032830, RC2NS070340, R01NS067305 and RC2GM093080), the Wellcome Trust (085475/B/08/Z, 085475/Z/08/Z, 084702/Z/08/Z and 098051), the UK MS Society (857/07, 861/07, 862/07, 894/08, 898/08 and 955/11), the UK Medical Research Council (G0700061), Naomi Branson, the Sainsbury Foundation, NMSS (RG 4198-A-1 and 4680-A-1, FG 1938-A-1, JF2138A1, JF-2137A4 and South Florida chapter), the Cambridge National Institute for Health Research (NIHR) British Research Council (BRC), DeNDRon, the Bibbi and Niels Jensens Foundation, the Swedish Brain Foundation, the Swedish Research and County Council, the Knut and Alice Wallenberg Foundation, the Swedish Heart-Lung Foundation, the AFA Foundation, the Foundation for Strategic Research, the Stockholm County Council (592229), the Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet, the Swedish Council for Working Life and Social Research, INSERM, ARSEP, AFM, GIS-IBISA, BMBF, KKNMS (01GI0917), Deutsche Forschungsgemeinschaft (530/1-1), Munich Biotec Cluster M4, the Fidelity Biosciences Research Initiative, FWO-Vlaanderen, Research Fund KU Leuven (OT/11/087), the Belgian Neurological Society, the Belgian Charcot Foundation, Gemeinnutzige Hertie Stiftung, CRPPMS University Zurich, the Danish MS Society, the Danish Council for Strategic Research, the Center of Excellence for Disease Genetics of the Academy of Finland, the Sigrid Juselius Foundation, the Helsinki University Central Hospital Research Foundation, FISM (2011/R/14), Fondazione Cariplo (2010-0728), MIUR (PRIN08), CRT Foundation Turin, the Italian Ministry of Health (502/92), the Italian Foundation for Multiple Sclerosis, INSPE, the Multiple Sclerosis Association of Oslo, the Norwegian Research Council (143153 and 143410), the South-Eastern Norwegian Health Authorities (51852/ILM) and the Australian National Health and Medical Research Council (633275 and 1053756).