Trial reportThe Journal of rheumatology2015
Do Genetic Susceptibility Variants Associate with Disease Severity in Early Active Rheumatoid Arthritis?
Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph
Trial report in The Journal of rheumatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 8% of its field
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.
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.
Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Pooled it
- The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis.Psychosomatic medicineTrial
- Inflammatory cytokines mediate the common genetic and immunological background between rheumatoid arthritis and osteoporosis.Clinical rheumatology · 2026Article
- The genetic puzzle of rheumatoid arthritis: Causes, progression, and treatment.Biochemistry and biophysics reports · 2025Review
- Association betweenMedicina (Kaunas, Lithuania) · 2023Article
- Steroid hormone-related polymorphisms associate with the development of bone erosions in rheumatoid arthritis and help to predict disease progression: Results from the REPAIR consortium.Scientific reports · 2019Article
- Article
- Genetic and environmental risk factors for rheumatoid arthritis in a UK African ancestry population: the GENRA case-control study.Rheumatology (Oxford, England) · 2017Article
- Genetics of rheumatoid arthritis susceptibility, severity, and treatment response.Seminars in immunopathology · 2017Review
- Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease.Nature genetics · 2017Article
- Article
- HLA-DRB1 Amino Acid Positions 11/13, 71, and 74 Are Associated With Inflammation Level, Disease Activity, and the Health Assessment Questionnaire Score in Patients With Inflammatory Polyarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2016Article
- AbnormalJCI insight · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 3 countries.
Ian C ScottFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Frühling RijsdijkFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Jemma WalkerFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Jelmar QuistFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Sarah L SpainFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Rachael TanFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Sophia SteerFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Yukinori OkadaFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Soumya RaychaudhuriFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Andrew P CopeFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Cathryn M LewisFrom the Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, and Social, Genetic and Developmental Psychiatry (SGDP) Centre, Institute of Psychiatry, and Department of Rheumatology, King's College London, and Guy's Hospital, London, UK; Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo; Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.I.C. Scott, PhD, Clinical Research Fellow, Department of Medical and Molecular Genetics, and Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London, and Guy's Hospital; F. Rijsdijk, PhD, Reader, SGDP Centre, Institute of Psychiatry, King's College London; J. Walker, PhD, Statistical Geneticist; J. Quist, PhD, MSc, Student; S.L. Spain, PhD, Research Associate, Department of Medical and Molecular Genetics, King's College London, and Guy's Hospital; R. Tan, MRes, Core Medical Trainee, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; S. Steer, PhD, Consultant Rheumatologist, Department of Rheumatology, King's College Hospital; Y. Okada, PhD, Tenure Track Junior Associate Professor, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, and Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences; S. Raychaudhuri, PhD, Professor, Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; A.P. Cope, PhD, Professor, Academic Department of Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, King's College London; C.M. Lewis, PhD, Prof
Harvard University · USKing's College London · GBTokyo Medical and Dental University · JPGuy's and St Thomas' NHS Foundation Trust · GBKing's College Hospital · GBRIKEN Center for Integrative Medical Sciences · JP
Funding
Discovery and Functional Impact of Common and Rare Variants in RAR01AR063759 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Soumya Raychaudhuri · 2013 to 2026
$5.4MFine-mapping the MHC associations in rheumatoid arthritis from GWAS dataR01AR062886 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI RAYCHAUDHURI, SOUMYA · 2012 to 2013
$783kArthritis Research UK 19739Arthritis Research UK 20525Medical Research Council G1001516NIAMS NIH HHS R01 AR062886NIAMS NIH HHS R01 AR063759
Abstract
objectiveGenetic variants affect both the development and severity of rheumatoid arthritis (RA). Recent studies have expanded the number of RA susceptibility variants. We tested the hypothesis that these associated with disease severity in a clinical trial cohort of patients with early, active RA.
methodsWe evaluated 524 patients with RA enrolled in the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trials. We tested validated susceptibility variants - 69 single-nucleotide polymorphisms (SNP), 15 HLA-DRB1 alleles, and amino acid polymorphisms in 6 HLA molecule positions - for their associations with progression in Larsen scoring, 28-joint Disease Activity Scores, and Health Assessment Questionnaire (HAQ) scores over 2 years using linear mixed-effects and latent growth curve models.
resultsHLA variants were associated with joint destruction. The *04:01 SNP (rs660895, p = 0.0003), *04:01 allele (p = 0.0002), and HLA-DRβ1 amino acids histidine at position 13 (p = 0.0005) and valine at position 11 (p = 0.0012) significantly associated with radiological progression. This association was only significant in anticitrullinated protein antibody (ACPA)-positive patients, suggesting that while their effects were not mediated by ACPA, they only predicted joint damage in ACPA-positive RA. Non-HLA variants did not associate with radiograph damage (assessed individually and cumulatively as a weighted genetic risk score). Two SNP - rs11889341 (STAT4, p = 0.0001) and rs653178 (SH2B3-PTPN11, p = 0.0004) - associated with HAQ scores over 6-24 months.
conclusionHLA susceptibility variants play an important role in determining radiological progression in early, active ACPA-positive RA. Genome-wide and HLA-wide analyses across large populations are required to better characterize the genetic architecture of radiological progression in RA.
Indexed as
Genetic Predisposition to DiseasePolymorphism, Single NucleotideAdultAllelesAntirheumatic AgentsArthritis, RheumatoidDisease ProgressionFemaleGenetic Association StudiesGenotypeHLA-DRB1 ChainsHumansMaleMiddle AgedModels, TheoreticalSeverity of Illness IndexAntirheumatic AgentsHLA-DRB1 ChainsGENETICSHLA ANTIGENSOUTCOME MEASURESRADIOGRAPHYRHEUMATOID ARTHRITIS
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