Journal
NATURE GENETICS
Volume 43, Issue 8, Pages 761-U67Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.873
Keywords
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Categories
Funding
- Wellcome Trust [083948/Z/07/Z, 076113, 068545/Z/02]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [P01-052915, R01-AR046208]
- University of Texas at Houston Clinical and Translational Science [UL1RR024188]
- Cedars-Sinai General Clinical Research Centre [MO1-RR00425]
- Intramural Research Program
- NIAMS/US National Institutes of Health
- Rebecca Cooper Foundation (Australia)
- Arthritis Research UK [19536, 18797]
- Oxford Comprehensive Biomedical Research Centre [A91202]
- Arthritis Society (Canada)
- Lions Medical Research Foundation fellowship
- National Health and Medical Research Council (Australia)
- National Health and Medical Research Council (Australia) [566938, 569829]
- Australian Cancer Research Foundation
- Rebecca Cooper Medical Research Foundation
- Wolfson-Royal Society Merit Award
- National Institute for Health Research (NIHR)
- Oxford Musculoskeletal Biomedical Research Unit
- NIHR Thames Valley Comprehensive Local Research Network
- Medical Research Council [G0000934]
- Canadian Institutes for Health Research
- Canadian Foundation for Innovation
- Genome Canada through the Ontario Genomics Institute
- GlaxoSmithKline
- Karolinska Institutet
- Knut and Alice Wallenberg Foundation
- Ontario Innovation Trust
- Ontario Ministry for Research and Innovation
- Merck Co., Inc.
- Novartis Research Foundation
- Swedish Agency for Innovation Systems
- Swedish Foundation for Strategic Research
- Wellcome Trust [083948/Z/07/Z] Funding Source: Wellcome Trust
- MRC [G0901310, G19/2, G0000934, G0600705, G0800582] Funding Source: UKRI
- Medical Research Council [G0000934, G0600705, G19/2, G9817803B, G1000800g, G0901310, G0800582] Funding Source: researchfish
- National Institute for Health Research [PDA/02/06/016, NF-SI-0507-10379] Funding Source: researchfish
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Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 x 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 x 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.
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