Trial reportHuman molecular genetics2018
A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.
Open access · bronzeAbstract readClinical TrialMulticenter Study
In one paragraph
Trial report in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 5% 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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Replication and meta-analyses nominate numerous eosinophilic esophagitis risk genes.The Journal of allergy and clinical immunology · 2021Pooled it
- Rare variants in non-coding regulatory regions of the genome that affect gene expression in systemic lupus erythematosus.Scientific reports · 2019Trial
- Identification and evaluation of 41 risk loci for juvenile idiopathic arthritis informs precision medicine: mechanistic implications of DNA topology and an HLA-A*02:01-ERAP2 interaction.medRxiv : the preprint server for health sciences · 2026Article
- An overview on Sjögren's syndrome and systemic lupus erythematosus' genetics.Toxicology research · 2025Review
- Breaking research silos to achieve equitable precision medicine in rheumatology.Nature reviews. Rheumatology · 2025Review
- Article
- The 330 risk loci known for systemic lupus erythematosus (SLE): a review.Frontiers in lupus · 2024Article
- STAT4 gene polymorphisms in human diseases.Frontiers in immunology · 2024Review
- Immune Phenotype as a Biomarker for Systemic Lupus Erythematosus.Biomolecules · 2023Review
- A Summary on the Genetics of Systemic Lupus Erythematosus, Rheumatoid Arthritis, Systemic Sclerosis, and Sjögren's Syndrome.Clinical reviews in allergy & immunology · 2023Review
- Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies.Nature reviews. Rheumatology · 2023Review
- Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19.Translational research : the journal of laboratory and clinical medicine · 2022Article
- Systemic lupus erythematosus as a genetic disease.Clinical immunology (Orlando, Fla.) · 2022Article
- SCARF1-Induced Efferocytosis Plays an Immunomodulatory Role in Humans, and Autoantibodies Targeting SCARF1 Are Produced in Patients with Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Interferon pathway lupus risk alleles modulate risk of death from acute COVID-19.medRxiv : the preprint server for health sciences · 2021Article
- Review
- Global discovery of lupus genetic risk variant allelic enhancer activity.Nature communications · 2021Article
- Calcineurin and Systemic Lupus Erythematosus: The Rationale for Using Calcineurin Inhibitors in the Treatment of Lupus Nephritis.International journal of molecular sciences · 2021Review
- STAT4 Is Largely Dispensable for Systemic Lupus Erythematosus-like Autoimmune- and Foreign Antigen-Driven Antibody-Forming Cell, Germinal Center, and Follicular Th Cell Responses.ImmunoHorizons · 2021Article
- SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression.Nature communications · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
69 authors at 20 institutions in 10 countries.
Zubin H PatelImmunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Xiaoming LuImmunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Daniel MillerCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Carmy R ForneyCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Joshua LeeCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Arthur LynchCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Connor SchroederCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Lois ParksCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Albert F MagnusenCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Xiaoting ChenCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Mario PujatoCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Avery MaddoxCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Erin E ZollerCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Bahram NamjouCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Hermine I BrunnerDivision of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Michael HenricksonDivision of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Jennifer L HugginsDivision of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Adrienne H WilliamsCenter for Public Health Genomics and the Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Julie T ZieglerCenter for Public Health Genomics and the Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Mary E ComeauCenter for Public Health Genomics and the Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Miranda C MarionCenter for Public Health Genomics and the Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Stuart B GlennArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Adam AdlerArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Nan ShenCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Swapan K NathArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Anne M StevensCenter for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Barry I FreedmanSection on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Bernardo A Pons-EstelServicio de Reumatología, Sanatorio Parque, Rosario 2000, Santa Fe, Argentina.
Betty P TsaoDivision of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Chaim O JacobDepartment of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Diane L KamenDivision of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Elizabeth E BrownDivision of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, United States of America.
Gary S GilkesonDivision of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Graciela S AlarcónDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Javier MartinInstituto de Parasitologia y Biomedicina Lopez-Neyra, CSIC, Granada 18001-18016, Spain.
John D ReveilleRheumatology and Clinical Immunogenetics, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Juan-Manuel AnayaCenter for Autoimmune Diseases Research (CREA), Universidad del Rosario, Bogota 111711, Colombia.
Judith A JamesArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Kathy L SivilsArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Lindsey A CriswellDepartment of Medicine, Rosalind Russell/Ephraim P Engleman Rheumatology Research Center, University of California San Francisco, San Francisco, CA 94143-0500, USA.
Luis M ViláDivision of Rheumatology, Department of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA.
Michelle PetriDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
R Hal ScofieldArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Robert P KimberlyDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jeffrey C EdbergDepartment of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Rosalind Ramsey-GoldmanDivision of Rheumatology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
So-Young BangDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 04763, Korea.
Hye-Soon LeeDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 04763, Korea.
Sang-Cheol BaeDepartment of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul 04763, Korea.
Susan A BoackleDivision of Rheumatology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Deborah Cunninghame GrahamDivisions of Genetics/Molecular Medicine and Immunology, King's College London, Guy's Hospital, London SE1 9RT, UK.
Timothy J VyseDivisions of Genetics/Molecular Medicine and Immunology, King's College London, Guy's Hospital, London SE1 9RT, UK.
Joan T MerrillArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Timothy B NiewoldDivision of Rheumatology, Department of Pathology, New York University, New York, NY 10016, USA.
Hannah C AinsworthCenter for Public Health Genomics and the Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Earl D SilvermanDivision of Rheumatology, The Hospital for Sick Children, Hospital for Sick Research Institute, University of Toronto, Toronto, ON M5G 1X8, Canada.
Michael H WeismanDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Daniel J WallaceDivision of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Prithvi RajDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Joel M GuthridgeArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Patrick M GaffneyArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Jennifer A KellyArthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Marta E Alarcón-RiquelmeUnit of Chronic Inflammatory Diseases, Institute of Environmental Medicine, Karolinska Institutet, Stockholm 17167, Sweden.
Carl D LangefeldCenter for Public Health Genomics and the Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Edward K WakelandDepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Kenneth M KaufmanCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Matthew T WeirauchCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
John B HarleyCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Leah C KottyanCenter for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Cincinnati Children's Hospital Medical Center · USOklahoma Medical Research Foundation · USWake Forest University · USUniversity of Alabama at Birmingham · USHanyang University Seoul Hospital · KRMedical University of South Carolina · USCedars-Sinai Medical Center · USGuy's Hospital · GBThe University of Texas Southwestern Medical Center · USCentro Científico Tecnólogico - Rosario · ARInstituto de Parasitología y Biomedicina "López - Neyra" · ESJohns Hopkins University · USKarolinska Institutet · SENew York University · USNorthwestern University · USThe University of Texas Health Science Center at Houston · USUnited States Department of Veterans Affairs · USUniversidad del Rosario · COUniversity of California, San Francisco · USUniversity of Colorado Denver · US
Funding
Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0MTracking and Evaluation CoreU54GM104938 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Robert Hal Scofield · 2013 to 2026
$68.2MNorthwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8MNIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1MUAB Center for Clinical and Translational Science (CCTS)UL1TR001417 · NCATS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 2015 to 2018
$31.4MTECHNOLOGIES AND RESOURCES FOR CORE LABORATORIESU54MD007587 · NIMHD · UNIVERSITY OF PUERTO RICO MED SCIENCES · PI BENABE, JULIO E, LUCIANO, CARLOS A. · 2012 to 2018
$23.2MColorado Clinical and Translational Science Institute (UL1)UL1TR000154 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2012 to 2013
$20.4MProgram Project in the Genetics of SLEP01AR049084 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI KIMBERLY, ROBERT P. · 2002 to 2012
$12.7MThe Interplay of Sociodemographic and Genetic Factors in SLE Health DisparitiesP60AR053308 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CRISWELL, LINDSEY ANN · 2006 to 2016
$11.8MMultidisciplinary Clinical and Translational Science (MCTS) Program (UL1)UL1TR000150 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LLOYD-JONES, DONALD M · 2012 to 2013
$10.1MSOUTH CAROLINA CLINICAL & TRANSLATIONAL RESEARCH INSTITUTE (SCTR)UL1RR029882 · NCRR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BRADY, KATHLEEN T. · 2009 to 2011
$10.1MCincinnati Center for Clinical and Translational Sciences and TrainingUL1TR000077 · NCATS · UNIVERSITY OF CINCINNATI · PI HEUBI, JAMES E., TSEVAT, JOEL · 2012 to 2014
$9.9MBLRD VA I01 BX001834NCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1 TR000077NCATS NIH HHS UL1 TR000150NCATS NIH HHS UL1 TR000154NCATS NIH HHS UL1 TR001417NCATS NIH HHS UL1 TR001422NCATS NIH HHS UL1 TR002535NCRR NIH HHS S10 RR027015NCRR NIH HHS UL1 RR029882NHGRI NIH HHS R21 HG008186NHGRI NIH HHS U01 HG006828NHGRI NIH HHS U01 HG008666NIAID NIH HHS K24 AI078004NIAID NIH HHS P01 AI083194NIAID NIH HHS R01 AI024717NIAID NIH HHS R01 AI063274NIAID NIH HHS R21 AI070304NIAID NIH HHS U01 AI101934NIAID NIH HHS U01 AI130830NIAID NIH HHS U19 AI082714NIAMS NIH HHS K24 AR002138NIAMS NIH HHS N01 AR062277NIAMS NIH HHS P01 AR049084NIAMS NIH HHS P30 AR053483NIAMS NIH HHS P30 AR070155NIAMS NIH HHS P30 AR070549NIAMS NIH HHS P30 AR072579NIAMS NIH HHS P30 AR072582NIAMS NIH HHS P30 AR073750NIAMS NIH HHS P60 AR053308NIAMS NIH HHS P60 AR062755NIAMS NIH HHS P60 AR064464NIAMS NIH HHS R01 AR043274NIAMS NIH HHS R01 AR043727NIAMS NIH HHS R01 AR043814NIAMS NIH HHS R01 AR051545NIAMS NIH HHS R01 AR056360NIAMS NIH HHS R01 AR057172NIAMS NIH HHS R01 AR060366NIAMS NIH HHS R01 AR063124NIAMS NIH HHS R01 AR064820NIAMS NIH HHS R01 AR069572NIAMS NIH HHS R01 AR072212NIAMS NIH HHS R21 AR065626NIAMS NIH HHS RC2 AR058959NIDDK NIH HHS R01 DK107502NIGMS NIH HHS P20 GM103456NIGMS NIH HHS P30 GM103510NIGMS NIH HHS P30 GM110766NIGMS NIH HHS T32 GM063483NIGMS NIH HHS T32 GM105526NIGMS NIH HHS U54 GM104938NIMHD NIH HHS R01 MD007909NIMHD NIH HHS U54 MD007587NINDS NIH HHS R01 NS099068
Abstract
Systemic lupus erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared with the non-risk allele of rs11889341. We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1.
Indexed as
AllelesPolymorphism, GeneticQuantitative Trait LociFemaleHumansLupus Erythematosus, SystemicMaleRisk FactorsSTAT1 Transcription FactorSTAT4 Transcription FactorSTAT1 protein, humanSTAT1 Transcription FactorSTAT4 protein, humanSTAT4 Transcription Factor
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