Journal
NATURE COMMUNICATIONS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms8146
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Funding
- Arthritis Research UK [19536, 18797]
- NIHR Oxford comprehensive Biomedical Research Centre [A93081]
- NIHR Thames Valley collaborative research network
- National Ankylosing Spondylitis Society (UK)
- Arthritis Society of Canada
- National Institutes of Health/National Institute of Allergy and Infectious Diseases grant [1U01 AI09090-01]
- Inst. Carlos III, Spain [PI12/02587]
- European Union 'Fondos FEDER'
- Agence Nationale de la Recherche [ANR-11-IDEX-0005-02]
- Societe Francaise de Rhumatologie (SFR)
- Arthritis Foundation
- Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health
- National Health and Medical Research Council (Australia)
- Australian Research Council [FT130101709]
- Netherlands Organization for Scientific Research [016.126.354]
- National Institutes of Health [1R01AR062886-1]
- Australian Research Council [FT130101709] Funding Source: Australian Research Council
- Medical Research Council [MC_UU_12013/4] Funding Source: researchfish
- Versus Arthritis [20796, 19356] Funding Source: researchfish
- MRC [MC_UU_12013/4] Funding Source: UKRI
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Ankylosing spondylitis (AS) is a common, highly heritable, inflammatory arthritis for which HLA-B*27 is the major genetic risk factor, although its role in the aetiology of AS remains elusive. To better understand the genetic basis of the MHC susceptibility loci, we genotyped 7,264 MHC SNPs in 22,647 AS cases and controls of European descent. We impute SNPs, classical HLA alleles and amino-acid residues within HLA proteins, and tested these for association to AS status. Here we show that in addition to effects due to HLA-B*27 alleles, several other HLA-B alleles also affect susceptibility. After controlling for the associated haplotypes in HLA-B, we observe independent associations with variants in the HLA-A, HLA-DPB1 and HLA-DRB1 loci. We also demonstrate that the ERAP1 SNP rs30187 association is not restricted only to carriers of HLA-B*27 but also found in HLA-B*40:01 carriers independently of HLA-B*27 genotype.
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