ArticleAnnals of the rheumatic diseases2022
Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset.
Open access · hybridAbstract read
In one paragraph
Article in Annals of the rheumatic diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 5 pooled it
12.9field-weighted citation impact, top 1% 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
60 citing papers in PubMed, 5 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Identification of new overlapping and disease-specific genetic risk factors for rheumatoid arthritis and radiographic axial spondyloarthritis: a meta-analysis of three large European populations and functional characterization.Frontiers in immunology · 2026Pooled it
- Polymorphisms in STAT4 and PTPRC genes in rheumatoid arthritis: a Brazilian study and meta-analysis of susceptibility and TNFi response.Immunologic research · 2025Pooled it
- The Genomics/Genetics of Primary Biliary Cholangitis: The Case for a Functional SNP rs10893900 in ETS1/FLI1 and Review of the Literature.Clinical reviews in allergy & immunology · 2025Pooled it
- Genomic loci and molecular genetic mechanisms for hidradenitis suppurativa.The British journal of dermatology · 2025Pooled it
- Identifying shared genetic loci and common risk genes of rheumatoid arthritis associated with three autoimmune diseases based on large-scale cross-trait genome-wide association studies.Frontiers in immunology · 2023Pooled it
- Discovery of 5-fluoro-aminopyrimidine derivatives as dual BTK/FLT3 inhibitors for the treatment of rheumatoid arthritis.Molecular diversity · 2026Article
- Tissue-resident immune cells drive genetic risk in autoimmune and lung diseases.Nature immunology · 2026Article
- rs57494551 increases CXCR5 expression and IgMJournal of gastroenterology · 2026Article
- Long-Term Outcomes in Seronegative Rheumatoid Arthritis.Arthritis care & research · 2026Article
- Clinical and Pharmacogenetic Factors Associated with Response to JAK Inhibitors in Patients with Rheumatoid Arthritis: A Real-World Study ofPharmaceutics · 2026Article
- Influence of the shared epitope on the effectiveness of biologic antirheumatic agents in European patients with rheumatoid arthritis.RMD open · 2026Article
- Validation of a Genetic Risk Score Combined With Clinical Variables for Predicting Pulmonary Fibrosis in Early Rheumatoid Arthritis.Arthritis care & research · 2026Article
- Review
- How Genomic and Structural Context Could Shape JAK-STAT Variant Pathogenicity.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2026Article
- Multiomics Analyses Reveal an Essential Role of Tryptophan in Treatment of csDMARDs in Rheumatoid Arthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Integrating human plasma proteomes with genome-wide association data implicates novel proteins and drug targets for rheumatoid arthritis.Clinical proteomics · 2026Article
- In Silico Functional and Structural Analysis ofGenes · 2026Article
- Shared genetic architecture and potential comorbid mechanisms between rheumatoid arthritis and idiopathic pulmonary fibrosis.Clinical rheumatology · 2026Article
- Natural compounds for the treatment of rheumatoid arthritis based on the 'gut‑joint axis' (Review).Molecular medicine reports · 2026Review
- Exploring the genetic architecture of multiple long-term conditions using a genome-wide association study in the UK Biobank population.Scientific reports · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
81 authors at 18 institutions in 4 countries.
Saedis SaevarsdottirdeCODE genetics/Amgen, Reykjavik, Iceland saedis.saevarsdottir@decode.is kstefans@decode.is.ORCID http://orcid.org/0000-0001-9392-6184
Lilja StefansdottirdeCODE genetics/Amgen, Reykjavik, Iceland.
Patrick SulemdeCODE genetics/Amgen, Reykjavik, Iceland.
Gudmar ThorleifssondeCODE genetics/Amgen, Reykjavik, Iceland.
Egil FerkingstaddeCODE genetics/Amgen, Reykjavik, Iceland.
Gudrun RutsdottirdeCODE genetics/Amgen, Reykjavik, Iceland.
Bente GlintborgThe DANBIO registry, the Danish Rheumatologic Biobank and Copenhagen Center for Arthritis Research (COPECARE), Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.ORCID http://orcid.org/0000-0002-8931-8482
Helga WesterlindDivision of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-3380-5342
Gerdur GrondalFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Isabella C LoftDepartment of Clinical Immunology, Zealand University Hospital, Køge, Denmark.
Signe Bek SorensenMolecular Diagnostics and Clinical Research Unit, IRS-Center Sonderjylland, University Hospital of Southern Denmark, Aabenraa, Denmark.
Benedicte A LieDepartment of Medical Genetics, University of Oslo, Oslo, Norway.
Mikael BrinkDepartment of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden.
Lisbeth ÄrlestigDepartment of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden.
Asgeir Orn ArnthorssondeCODE genetics/Amgen, Reykjavik, Iceland.
Eva BaecklundDepartment of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden.
Karina BanasikNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Steffen BankMolecular Diagnostics and Clinical Research Unit, IRS-Center Sonderjylland, University Hospital of Southern Denmark, Aabenraa, Denmark.
Lena I BjorkmanDepartment of Rheumatology and Inflammation research, University of Gothenburg, Gothenburg, Sweden.
Torkell EllingsenOPEN Explorative Network, University of Southern Denmark, Odense, Denmark.ORCID http://orcid.org/0000-0003-0426-4962
Christian ErikstrupDepartment of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
Oleksandr FreiNORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Inger GjertssonDepartment of Rheumatology and Inflammation Research, Gothenburg University, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-9301-4844
Daniel F GudbjartssondeCODE genetics/Amgen, Reykjavik, Iceland.
Sigurjon A GudjonssondeCODE genetics/Amgen, Reykjavik, Iceland.
Gisli H HalldorssondeCODE genetics/Amgen, Reykjavik, Iceland.
Oliver HendricksDanish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark.
Jan HillertDepartment of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Estrid HogdallDepartment of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Søren JacobsenDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-5654-4993
Dorte Vendelbo JensenDepartment of Rheumatology, Center for Rheumatology and Spine Diseases, Gentofte and Herlev Hospital, Rønne, Denmark.
Helgi JonssonFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Alf KastbomDepartment of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.ORCID http://orcid.org/0000-0001-7187-1477
Ingrid KockumDepartment of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Salome KristensenDepartment of Rheumatology, Aalborg University Hospital, Aalborg, Denmark.ORCID http://orcid.org/0000-0001-5812-5234
Helga KristjansdottirCenter for Rheumatology Research, Landspitali, the National University Hospital of Iceland, Reykjavik, Iceland.
Margit H LarsenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Asta LinauskasDepartment of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Ellen-Margrethe HaugeDepartment of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
Anne G LoftDepartment of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
Bjorn R LudvikssonFaculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
Sigrun H LunddeCODE genetics/Amgen, Reykjavik, Iceland.
Thorsteinn MarkussondeCODE genetics/Amgen, Reykjavik, Iceland.
Gisli MassondeCODE genetics/Amgen, Reykjavik, Iceland.
Pall MelsteddeCODE genetics/Amgen, Reykjavik, Iceland.
Kristjan H S MooredeCODE genetics/Amgen, Reykjavik, Iceland.
Heidi MunkOPEN Explorative Network, University of Southern Denmark, Odense, Denmark.ORCID http://orcid.org/0000-0002-2212-6283
Kaspar R NielsenDepartment of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
Gudmundur L NorddahldeCODE genetics/Amgen, Reykjavik, Iceland.
Asmundur OddssondeCODE genetics/Amgen, Reykjavik, Iceland.
Thorunn A OlafsdottirdeCODE genetics/Amgen, Reykjavik, Iceland.
Pall I OlasondeCODE genetics/Amgen, Reykjavik, Iceland.
Tomas OlssonDepartment of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Sisse Rye OstrowskiDepartment of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Kim Hørslev-PetersenDanish Hospital for Rheumatic Diseases, University Hospital of Southern Denmark, Sønderborg, Denmark.
Solvi RognvaldssondeCODE genetics/Amgen, Reykjavik, Iceland.
Helga SannerSection of Rheumatology, Oslo University Hospital, Oslo, Norway.
Gilad N SilberbergDivision of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Hreinn StefanssondeCODE genetics/Amgen, Reykjavik, Iceland.
Erik SørensenDepartment of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Inge J SørensenCopenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Rigshospitalet, Copenhagen, Denmark.
Carl TuressonRheumatology, Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.ORCID http://orcid.org/0000-0002-3805-2290
Thomas BergmanDivision of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Lars AlfredssonDepartment of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Tore K KvienUniversity of Oslo, Oslo, Norway.
Søren BrunakNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Kristján SteinssonCenter for Rheumatology Research, Landspitali, the National University Hospital of Iceland, Reykjavik, Iceland.
Vibeke AndersenMolecular Diagnostics and Clinical Research Unit, IRS-Center Sonderjylland, University Hospital of Southern Denmark, Aabenraa, Denmark.ORCID http://orcid.org/0000-0002-0127-2863
Ole A AndreassenNORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Solbritt Rantapää-DahlqvistDepartment of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden.ORCID http://orcid.org/0000-0001-8259-3863
Merete Lund HetlandThe DANBIO registry, the Danish Rheumatologic Biobank and Copenhagen Center for Arthritis Research (COPECARE), Centre for Rheumatology and Spine Diseases, Centre of Head and Orthopaedics, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.ORCID http://orcid.org/0000-0003-4229-6818
Lars KlareskogDivision of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-9601-6186
Johan AsklingDivision of Clinical Epidemiology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-0433-0616
Leonid PadyukovDivision of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Ole Bv PedersenDepartment of Clinical Immunology, Zealand University Hospital, Køge, Denmark.
Unnur ThorsteinsdottirdeCODE genetics/Amgen, Reykjavik, Iceland.
Ingileif JonsdottirdeCODE genetics/Amgen, Reykjavik, Iceland.
Kari StefanssondeCODE genetics/Amgen, Reykjavik, Iceland saedis.saevarsdottir@decode.is kstefans@decode.is.
Members of the DBDS Genomic Consortium
Danish RA Genetics Working Group
Swedish Rheumatology Quality Register Biobank Study Group (SRQb)
deCODE Genetics (Iceland) · ISUniversity of Copenhagen · DKKarolinska Institutet · SEOslo University Hospital · NOUniversity of Southern Denmark · DKUmeå University · SEUniversity of Iceland · ISZealand University Hospital Køge · DKAarhus University Hospital · DKCopenhagen University Hospital · DKLinköping University · SEUppsala University · SEAarhus University · DKLund University · SEAalborg University Hospital · DKHerlev Hospital · DKSygehus Sønderjylland · DKUniversity of Gothenburg · SE
Funding
Medical Research Council MC_PC_17228Medical Research Council MC_QA137853
Abstract
objectivesTo find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets.
methodsWe performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and ~1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen).
resultsWe found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in
conclusionSequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
Indexed as
Arthritis, RheumatoidGenome-Wide Association StudyGenetic Predisposition to DiseaseHumansInterferon-alphaJanus KinasesProtein Tyrosine Phosphatase, Non-Receptor Type 22ProteomicsSignal TransductionSTAT Transcription FactorsInterferon-alphaJanus KinasesProtein Tyrosine Phosphatase, Non-Receptor Type 22PTPN22 protein, humanSTAT Transcription Factorsautoantibodiespolymorphism, geneticrheumatoid arthritis
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY-NC
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.