期刊
NATURE GENETICS
卷 47, 期 10, 页码 1107-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3395
关键词
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资金
- US National Institutes of Health [NS049477, NS26799, R01NS032830, RC2NS070340, R01NS067305, RC2GM093080]
- Wellcome Trust [085475/B/08/Z, 085475/Z/08/Z, 084702/Z/08/Z, 098051]
- UK MS Society [857/07, 861/07, 862/07, 894/08, 898/08, 955/11]
- UK Medical Research Council [G0700061]
- NMSS (South Florida chapter) [RG 4198-A-1, 4680-A-1, FG 1938-A-1, JF2138A1, JF-2137A4]
- Cambridge National Institute for Health Research (NIHR) British Research Council (BRC)
- DeNDRon
- Bibbi and Niels Jensens Foundation
- Swedish Brain Foundation
- Swedish Research and County Council
- Knut and Alice Wallenberg Foundation
- Swedish Heart-Lung Foundation
- AFA Foundation
- Foundation for Strategic Research
- Stockholm County Council [592229]
- Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet
- 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
- Fidelity Biosciences Research Initiative
- FWO-Vlaanderen
- Research Fund KU Leuven [OT/11/087]
- Belgian Neurological Society
- Belgian Charcot Foundation
- Gemeinnutzige Hertie Stiftung
- CRPPMS University Zurich
- Danish MS Society
- Danish Council for Strategic Research
- Center of Excellence for Disease Genetics of the Academy of Finland
- Sigrid Juselius Foundation
- FISM [2011/R/14]
- Fondazione Cariplo [2010-0728]
- MIUR (PRIN)
- CRT Foundation Turin
- Italian Ministry of Health [502/92]
- Italian Foundation for Multiple Sclerosis
- Multiple Sclerosis Association of Oslo
- Norwegian Research Council [143153, 143410]
- South-Eastern Norwegian Health Authorities [51852/ILM]
- Australian National Health and Medical Research Council [633275, 1053756]
- INSPE
- Helsinki University Central Hospital Research Foundation
- MRC [G0700061, G0000934] Funding Source: UKRI
- Wellcome Trust [084702/Z/08/Z] Funding Source: Wellcome Trust
- Medical Research Council [G0700061, G0000934] Funding Source: researchfish
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.
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