Evidence map›Paper›PMID 25994336›Full record

ArticleNature communications2015

Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1.

Adrian Cortes, Sara L Pulit, Paul J Leo, Jenny J Pointon, Philip C Robinson, Michael H Weisman, Michael Ward, Lianne S Gensler, Xiaodong Zhou, Henri-Jean Garchon and 38 more

Open access · goldAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 5 pooled it
20.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

160 citing papers in PubMed, 5 syntheses or guidelines pooled it, 317 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Trial
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Global epidemiology of spondyloarthritis.Nature reviews. Rheumatology · 2025
    Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

48 authors at 20 institutions in 15 countries.

Adrian CortesUniversity of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane 4102, Australia.
Sara L PulitDepartment of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584, The Netherlands.
Paul J LeoUniversity of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane 4102, Australia.
Jenny J PointonNIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK.
Philip C RobinsonUniversity of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane 4102, Australia.
Michael H WeismanDepartment of Medicine/Rheumatology, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Michael WardIntramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892-1468, USA.
Lianne S GenslerDepartment of Medicine/Rheumatology, University of California, San Francisco, California 94143, USA.
Xiaodong ZhouDepartment of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Henri-Jean Garchon1] INSERM UMR 1173, Université de Versailles Saint Quentin en Yvelines, Laboratoire d'excellence Inflamex, Saint-Quentn-En-Yvelines 78180, France [2] Genetics Division, Hôpital Ambroise Paré, AP-HP, and Université de Versailles Saint Quentin en Yvelines, Boulogne-Billancourt 78180, France.
Gilles ChiocchiaINSERM UMR 1173, Université de Versailles Saint Quentin en Yvelines, Laboratoire d'excellence Inflamex, Saint-Quentn-En-Yvelines 78180, France.
Johannes Nossent1] School of Medicine, University of Western Australia, Perth, WA 6009, Australia [2] Department of Rheumatology, Sir Charles Gairdner Hospital, Perth, WA 6009, Australia.ORCID 0000000228337997
Benedicte A Lie1] Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo 0310, Norway [2] Department of Immunology, Oslo University Hospital, Oslo 0310, Norway.
Øystein FørreDepartment of Rheumatology, Oslo University Hospital, and University of Oslo, Oslo 0310, Norway.
Jaakko Tuomilehto1] Department of Chronic Disease Prevention, National Institute for Health and Welfare, 00271 Helsinki, Finland [2] Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria [3] Diabetes Research Group, King Abdulaziz University, 21589 Jeddah, Saudi Arabia.
Kari LaihoDepartment of Medicine, Paijat-Hame Central Hospital, Lahti, Finland.
Linda A BradburyUniversity of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane 4102, Australia.
Dirk Elewaut1] Department of Rheumatology, Gent University Hospital, Gent 9052, Belgium [2] VIB Inflammation Research Center, Ghent University, Gent 9052, Belgium.
Ruben Burgos-VargasDepartment of Rheumatology, Hospital General de Mexico and Universidad Nacional Autonoma de Mexico, Mexico City 06726, Mexico.
Simon StebbingsDepartment of Medicine, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand.
Louise AppletonNIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK.
Claire FarrahNIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK.
Jonathan LauNIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK.
Nigil HaroonDivision of Rheumatology, Toronto Western Hospital, University of Toronto, Toronto M5T2S8, Canada.
Juan MuleroDepartment of Rheumatology, Hospital Puerta de Hierro, Madrid 28222, Spain.
Francisco J BlancoDepartment of Rheumatology, Complejo Hospitalario La Coruña, INIBIC, La Coruña 15006, Spain.
Miguel A Gonzalez-GayDepartment of Rheumatology, Hospital Marques de Valcecillas, IFIMAV, Santander 39008, Spain.
C Lopez-Larrea1] Department of Immunology, Hospital Universitario Central de Asturias, Oviedo 33011, Spain [2] Fundación Renal 'Iñigo Álvarez de Toledo', Madrid 33011, Spain.
Paul BownessNIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK.
Karl GaffneyDepartment of Rheumatology, Norfolk and Norwich University Hospital, Norwich NR4 7UY, UK.
Hill GastonDepartment of Medicine, University of Cambridge, Addenbrookes Hospital, Cambridge CB2 0SP, UK.
Dafna D Gladman1] Division of Rheumatology, University of Toronto, Toronto, ON M4N 3M5, Canada [2] Toronto Western Research Institute, Toronto ON M4N 3M5, Canada [3] Psoriatic Arthritis Program, University Health Network, Toronto ON M4N 3M5, Canada.
Proton RahmanMemorial University of Newfoundland, Newfoundland NL A1B 3X9, Canada.
Walter P MaksymowychDepartment of Medicine, University of Alberta, Alberta T6G 2R7, Canada.
J Bart A CrusiusDepartment of Medical Microbiology and Infection Control, Laboratory of Immunogenetics, VU University Medical Center, Amsterdam 1081 BT, The Netherlands.
Irene E van der Horst-BruinsmaDepartment of Rheumatology, VU University Medical Centre, Amsterdam 1081 BT, Netherlands.
Raphael Valle-OñateSpondyloarthropaty Group-Division of Rheumatology, Hospital Militar Central/Universidad de La Sabana, Transversal 3 # 49-00, Bogotá, NA, Colombia.
Consuelo Romero-SánchezSpondyloarthropaty Group-Division of Rheumatology, Hospital Militar Central/Universidad de La Sabana, Transversal 3 # 49-00, Bogotá, NA, Colombia.
Inger Myrnes HansenHelgelandssykehuset, 8613 Mo i Rana, Norway.
Fernando M Pimentel-SantosChronic Diseases Research Centre (CEDOC), Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa 1169-056, Portugal.
Robert D InmanDivision of Rheumatology, Toronto Western Hospital, University of Toronto, Toronto M5T2S8, Canada.
Javier MartinInstituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones-Científicas, Granada 18100, Spain.
Maxime Breban1] INSERM UMR 1173, Université de Versailles Saint Quentin en Yvelines, Laboratoire d'excellence Inflamex, Saint-Quentn-En-Yvelines 78180, France [2] Division of Rheumatology, Hôpital Ambroise Paré, AP-HP, and Université de Versailles Saint Quentin en Yvelines, Boulogne-Billancourt 92100, France.
Bryan Paul WordsworthNIHR Oxford Musculoskeletal Biomedical Research Unit, Nuffield Orthopaedic Centre, Headington, Oxford OX3 7LD, UK.
John D ReveilleDepartment of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
David M Evans1] University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane 4102, Australia [2] MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK [3] School of Social and Community Medicine, University of Bristol, Bristol, UK.
Paul I W de Bakker1] Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht 3584, The Netherlands [2] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Matthew A BrownUniversity of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane 4102, Australia.
Nuffield Orthopaedic Centre · GBThe University of Queensland · AUInserm · FRUniversity of Toronto · CAAmsterdam UMC Location Vrije Universiteit Amsterdam · NLOslo University Hospital · NOThe University of Texas Health Science Center at Houston · USUniversidad de La Sabana · COUniversity Medical Center Utrecht · NLCedars-Sinai Medical Center · USComplexo Hospitalario Universitario A Coruña · ESConsejo Superior de Investigaciones Científicas · ESFundación Marques de Valdecilla · ESGhent University Hospital · BEHospital General de México · MXHospital Universitario Central de Asturias · ESHospital Universitario Puerta de Hierro Majadahonda · ESMemorial University of Newfoundland · CANational Institutes of Health · USNordland Hospital Trust · NO

Funding

Clinical Support Services for the NIAMS Intramural Research ProgramZIDAR041180 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI COLBERT, ROBERT · 2009 to 2025
$119.2M
Outcomes in Rheumatic DiseasesZIAAR041153 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI WARD, MICHAEL · 2009 to 2020
$12.6M
The Genetic Basis of AS SusceptibilityP01AR052915 · NIAMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BROWN, MATTHEW A · 2006 to 2016
$10.9M
Fine-mapping the MHC associations in rheumatoid arthritis from GWAS dataR01AR062886 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI RAYCHAUDHURI, SOUMYA · 2012 to 2013
$783k
Arthritis Research UK 18797Arthritis Research UK 19536Intramural NIH HHSMedical Research Council MC_UU_12013/4NIAID NIH HHS 1U01AI09090-01NIAMS NIH HHS 1R01AR062886-1NIAMS NIH HHS P01 AR052915NIAMS NIH HHS R01 AR062886Versus Arthritis 19356Versus Arthritis 20796Wellcome Trust 084767
6 · The paper itself

Abstract

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.

Indexed as

AminopeptidasesCase-Control StudiesEpistasis, GeneticGenetic Predisposition to DiseaseHLA-B27 AntigenHLA-B40 AntigenHumansMajor Histocompatibility ComplexMinor Histocompatibility AntigensPolymorphism, Single NucleotideSpondylitis, AnkylosingAminopeptidasesERAP1 protein, humanHLA-B27 AntigenHLA-B40 AntigenMinor Histocompatibility Antigens

Identifiers

PMID25994336
PMCPMC4443427
OpenAlexW1557481987

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.