SynthesisAnnals of the rheumatic diseases2025
Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Annals of the rheumatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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
5 citing papers in PubMed.
- A Versatile Anti-CXCR5 Monoclonal Antibody (CxCurrent issues in molecular biology · 2026Article
- Genome-wide association analyses highlight the neuronal contribution to multiple sclerosis susceptibility.Nature genetics · 2026Article
- Systematic dysregulation of immune-related alternative polyadenylation in systemic lupus erythematosus contributes to patient stratification.Journal of translational autoimmunity · 2026Article
- The power of genetics in decoding Sjögren's disease: current status and future development.Current opinion in immunology · 2026Review
- GWAS highlights the neuronal contribution to multiple sclerosis susceptibility.medRxiv : the preprint server for health sciences · 2024Article
Corrections and comments
- Update ofVariants in the2023
Authors and funding
83 authors.
Mandi M WileyGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
Marcin RadziszewskiGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Bhuwan KhatriGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
Michelle L JoachimsGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA; Arthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, OK, USA.
Kandice L TessneerGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
Anna M StolarczykGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
Songyuan YaoGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
James LiGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Cherilyn Pritchett-FrazeeGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
Audrey A JohnstonArthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, OK, USA.
Astrid RasmussenGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
Juan-Manuel AnayaUniversidad de la Costa, Barranquilla, Colombia.
Lara A AqrawiKristiania University College, Oslo, Norway; University of Oslo, Oslo, Norway.
Sang-Cheol BaeDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Hanyang University Institute for Rheumatology Research and Hanyang Institute of Bioscience and Biotechnology, Seoul, Republic of Korea.
Eva BaecklundDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Albin BjörkKarolinska Institutet, Stockholm, Sweden.
Johan G BrunHaukeland University Hospital, Bergen, Norway; Broegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.
Sara Magnusson BucherÖrebro University, Örebro, Sweden.
Nick DandDepartment of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, UK.
Maija-Leena ElorantaDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Fiona EngelkeHannover Medical School, Hannover, Germany.
Helena Forsblad-d'EliaUniversity of Gothenburg, Gothenburg, Sweden; Umeå Universitet, Umeå, Sweden.
Cecilia FugmannDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Stuart B GlennGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
Chen GongDepartment of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, UK.
Jacques-Eric GottenbergHôspitaux Universitaires de Strasbourg, Strasbourg, France; Université de Strasbourg, Strasbourg, France; Regenerative NanoMedicine, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France.
Daniel HammenforsHaukeland University Hospital, Bergen, Norway; Broegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.
Juliana Imgenberg-KreuzDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Janicke Liaaen JensenUniversity of Oslo, Oslo, Norway.
Svein Joar Auglænd JohnsenStavanger University Hospital, Stavanger, Norway.
Malin V JonssonBroegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.
Jennifer A KellyGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA.
Sharmily KhanamArthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, OK, USA.
Kwangwoo KimKyung Hee University, Seoul, Republic of Korea.
Marika KvarnströmKarolinska Institutet, Stockholm, Sweden; Academic Specialist Center, Center for Rheumatology, Stockholm Health Services, Stockholm, Sweden.
Thomas MandlSkane University Hospital Malmö, Lund University, Malmö, Sweden.
Javier MartínInstituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain.
David L MorrisDepartment of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, UK.
Gaetane NocturneUniversité Paris-Saclay, Le Kremlin Bicêtre, Paris, France; Assistance Publique - Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, Paris, France.
Katrine Brække NorheimBroegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway; Stavanger University Hospital, Stavanger, Norway.
Peter OlssonSkane University Hospital Malmö, Lund University, Malmö, Sweden.
Øyvind PalmOslo University Hospital, Oslo, Norway.
Jacques-Olivier PersLBAI, UMR1227, University of Brest, INSERM, Brest, France; CHU de Brest, Brest, France.
Nelson L RhodusUniversity of Minnesota, Minneapolis, MN, USA.
Christopher SjöwallDepartment of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden.
Kathrine SkarsteinHaukeland University Hospital, Bergen, Norway; Broegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.
Kimberly E TaylorUniversity of California San Francisco, San Francisco, CA, USA.
Phil TomblesonDepartment of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, UK; NIHR GSTFT/KCL Biomedical Research Centre, London, UK.
Gudny Ella ThorlaciusKarolinska Institutet, Stockholm, Sweden.
Swamy R VenuturupalliCedars-Sinai Medical Center, Los Angeles, CA, USA.
Edward M VitalLeeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; NIHR Leeds Musculoskeletal Biomedical Research Centre, Leeds Teaching Hospital NHS Trust, Leeds, UK.
Daniel J WallaceCedars-Sinai Medical Center, Los Angeles, CA, USA.
Lida RadfarCollege of Dentistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Michael T BrennanAtrium Health Carolinas Medical Center, Charlotte, NC, USA; Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Judith A JamesUniversity of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; Arthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, OK, USA.
R Hal ScofieldUniversity of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; Arthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, OK, USA; US Department of Veteran Affairs Medical Center, Oklahoma City, OK, USA.
Patrick M GaffneyGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Lindsey A CriswellUniversity of California San Francisco, San Francisco, CA, USA; National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Roland JonssonBroegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.
Silke AppelBroegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.
Per ErikssonDepartment of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden.
Simon J BowmanUniversity Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Roald OmdalBroegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway; Stavanger University Hospital, Stavanger, Norway.
Lars RönnblomDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Blake M WarnerSalivary Disorders Unit and NIDCR Sjögren's Disease Clinic, National Institute of Dental and Craniofacial Research, Bethesda, MD, USA.
Maureen RischmuellerThe Queen Elizabeth Hospital and Medical School, University of Adelaide, SA, Australia.
Torsten WitteHannover Medical School, Hannover, Germany.
A Darise FarrisUniversity of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; Arthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, OK, USA.
Xavier MarietteUniversité Paris-Saclay, Le Kremlin Bicêtre, Paris, France; Assistance Publique - Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, Paris, France.
Caroline H ShiboskiUniversity of California San Francisco, San Francisco, CA, USA.
Sjögren’s International Collaborative Clinical Alliance (SICCA)
Marie Wahren-HerleniusKarolinska Institutet, Stockholm, Sweden; Broegelmann Research Laboratory, Department of Clinical Sciences, University of Bergen, Bergen, Norway.
Marta E Alarcón-RiquelmeKarolinska Institutet, Stockholm, Sweden; GENYO, Center for Genomics and Oncological Research Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain.
PRECISESADS Clinical Consortium
Wan-Fai NgNIHR Newcastle Biomedical Research Centre and NIHR Newcastle Clinical Research Facility, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK; University College Cork, Cork, Ireland.
UK Primary Sjögren’s Syndrome Registry
Kathy L SivilsArthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, OK, USA.
Joel M GuthridgeUniversity of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; Arthritis and Clinical Immunology Research Program, OMRF, Oklahoma City, OK, USA.
Indra AdriantoHenry Ford Health, Detroit, MI, USA; Michigan State University, East Lansing, MI, USA; Henry Ford Health + Michigan State University Health Sciences, East Lansing, MI, USA.
Timothy J VyseDepartment of Medical and Molecular Genetics, School of Basic and Medical Biosciences, King's College London, London, UK.
Betty P TsaoMedical University of South Carolina, Charleston, SC, USA.
Gunnel NordmarkDepartment of Medical Sciences, Uppsala University, Uppsala, Sweden.
Christopher J LessardGenes and Human Disease Research Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK, USA; University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. Electronic address: chris-lessard@omrf.org.
Funding
Targeting the p53 pathway for reversal of oral premalignancyP50CA097007 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LEE, HO-YOUNG · 2002 to 2012
$26.1MUT M.D. Anderson Cancer Center SPORE in MelanomaP50CA093459 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GRIMM, ELIZABETH A · 2004 to 2014
$23.7MOklahoma Rheumatic Disease Research Cores Center (Overall Application)P30AR073750 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JUDITH A JAMES · 2018 to 2026
$8.5MRESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2MPathogenic B Cells in Sjogren's SyndromeP50AR060804 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI SIVILS, KATHY L. · 2011 to 2015
$7.9MCreating a National Resource for Genetic Research in Behavioral & Health SciencesRC2AG036495 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WEIR, DAVID R. · 2009 to 2010
$7.4MGenome Wide Association Coordinating CenterU01HG004446 · NHGRI · UNIVERSITY OF WASHINGTON · PI WEIR, BRUCE S. · 2007 to 2011
$6.6MMolecular Epidemiology of Head and Neck CancerR01ES011740 · NIEHS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WEI, QINGYI · 2001 to 2012
$6.3MExpanding a National Resource for Genetic Research in Behavioral & Health ScienceRC4AG039029 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WEIR, DAVID R. · 2010 to 2010
$6.0MAutoimmune Drivers and Protectors Team Science (ADAPTS)U01AI176244 · NIAID · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI JUDITH A JAMES, Jeffrey C Rathmell · 2023 to 2026
$5.1MSjögren's International Collaborative Clinical Alliance Next Generation Studies (SICCA-NextGen)U01DE028891 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SHIBOSKI, CAROLINE HELENE · 2020 to 2024
$4.0MDiscovery and Characterization of Genetic Risk Loci in Sjogren's SyndromeR01AR073855 · NIAMS · OKLAHOMA MEDICAL RESEARCH FOUNDATION · PI LESSARD, CHRISTOPHER J · 2020 to 2024
$3.7MIntramural NIH HHS Z01 DE000704NCI NIH HHS P50 CA093459NCI NIH HHS P50 CA097007NCI NIH HHS R01 CA133996NHGRI NIH HHS HHSN268200782096CNHGRI NIH HHS U01 HG004446NHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201200008CNHLBI NIH HHS HHSN268201200008INIAID NIH HHS U01 AI176244NIAID NIH HHS UM1 AI144292NIAMS NIH HHS P30 AR070155NIAMS NIH HHS P30 AR073750NIAMS NIH HHS P50 AR060804NIAMS NIH HHS R01 AR065953NIAMS NIH HHS R01 AR071410NIAMS NIH HHS R01 AR071947NIAMS NIH HHS R01 AR073855NIAMS NIH HHS R01 AR074310NIAMS NIH HHS R01 AR083553NIAMS NIH HHS R21 AR079089NIAMS NIH HHS R33 AR076803NIAMS NIH HHS R61 AR076803NIA NIH HHS RC2 AG036495NIA NIH HHS RC4 AG039029NIDCR NIH HHS N01 DE032636NIDCR NIH HHS R03 DE029800NIDCR NIH HHS U01 DE028891NIEHS NIH HHS R01 ES011740
Abstract
objectivesSjögren's disease (SjD) and systemic lupus erythematosus (SLE) share genetic risk at the DDX6-CXCR5 locus (11q23.3). Identifying and functionally characterising shared SNPs spanning this locus can provide new insights into common genetic mechanisms of autoimmunity.
methodsTransdisease meta-analyses, fine-mapping, and bioinformatic analyses prioritised shared likely functional single nucleotide polymorphisms (SNPs) for allele-specific and cell type-specific functional interrogation using electromobility shift, luciferase reporter, and quantitative chromatin conformation capture assays and clustered regularly interspaced short palindromic repeat (CRISPR) gene regulation.
resultsFive shared SNPs were identified as likely functional in primary human immune cells, salivary gland and kidney tissues: rs57494551, rs4936443, rs4938572, rs7117261, and rs4938573. All 5 SNPs exhibited cell type-specific and allele-specific effects on nuclear protein binding affinity and enhancer/promoter regulatory activity in immune, salivary gland epithelial, and kidney epithelial cell models. Mapping of chromatin-chromatin interactions revealed a chromatin regulatory network that expanded beyond DDX6 and CXCR5 to include PHLDB1, lnc-PHLDB1-1, BCL9L, TRAPPC4, among others. Coalescence of functional assays and multiomic data analyses indicated that these SNPs likely modulate the activity of 3 regulatory regions: intronic rs57494551 regulatory region, intergenic SNP haplotype (rs4938572, rs4936443, and rs7117261) regulatory region, and rs4938573 regulatory region upstream of the CXCR5 promoter.
conclusionsShared genetic susceptibly at the DDX6-CXCR5 locus in SjD and SLE likely alters common mechanisms of autoimmunity, including interferon signalling (DDX6), autophagy (TRAPPC4), and lymphocytic infiltration of disease-target tissues (CXCR5). Further, using multiomic data from patients with SjD, combined with bioinformatic and in vitro functional studies, can provide mechanistic insights into how genetic risk influences the biological pathways that drive complex autoimmunity.
Indexed as
DEAD-box RNA HelicasesLupus Erythematosus, SystemicReceptors, CXCR5Salivary GlandsSjogren's SyndromeAutoimmune DiseasesGene Regulatory NetworksGenetic Predisposition to DiseaseHumansKidneyPolymorphism, Single NucleotideCXCR5 protein, humanDEAD-box RNA HelicasesReceptors, CXCR5
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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 Socratic graph.