Evidence map›Paper›PMID 39679859›Full record

SynthesisArthritis & rheumatology (Hoboken, N.J.)2025

Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.

Catherine Zhu, Younghun Han, Jinyoung Byun, Xiangjun Xiao, Simon Rothwell, Frederick W Miller, Ingrid E Lundberg, Peter K Gregersen, Jiri Vencovsky, Vikram R Shaw and 22 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in Arthritis & rheumatology (Hoboken, N.J.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Review
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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

32 authors.

Catherine ZhuBaylor College of Medicine, Houston, Texas.ORCID https://orcid.org/0000-0002-4939-515X
Younghun HanBaylor College of Medicine, Houston, Texas.ORCID https://orcid.org/0000-0001-5048-8479
Jinyoung ByunBaylor College of Medicine, Houston, Texas.ORCID https://orcid.org/0000-0001-8579-1435
Xiangjun XiaoBaylor College of Medicine, Houston, Texas.
Simon RothwellThe University of Manchester, Manchester, United Kingdom.ORCID https://orcid.org/0000-0003-2123-9902
Frederick W MillerNational Institute of Environmental Health Sciences, NIH, Bethesda, Maryland.ORCID https://orcid.org/0000-0003-2831-9593
Ingrid E LundbergKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.ORCID https://orcid.org/0000-0002-6068-9212
Peter K GregersenThe Feinstein Institute, Manhasset, New York.ORCID https://orcid.org/0000-0003-1613-1518
Jiri VencovskyCharles University, Prague, Czech Republic.ORCID https://orcid.org/0000-0002-0851-0713
Vikram R ShawBaylor College of Medicine, Houston, Texas.ORCID https://orcid.org/0000-0002-1172-5686
Neil McHughUniversity of Bath, Bath, United Kingdom.
Vidya LimayeUniversity of Adelaide, Adelaide, South Australia, Australia.
Albert Selva-O'CallaghanUniversitat Autonoma de Barcelona, Barcelona, Spain.ORCID https://orcid.org/0000-0003-2823-9761
Michael G HannaUniversity College London, London, United Kingdom.ORCID https://orcid.org/0000-0003-0825-4075
Pedro M MachadoUniversity College London, London, United Kingdom.ORCID https://orcid.org/0000-0002-8411-7972
Lauren M PachmanAnn & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Ann M ReedDuke University, Durham, North Carolina.ORCID https://orcid.org/0000-0002-4521-7647
Lisa G RiderNational Institute of Environmental Health Sciences, NIH, Bethesda, Maryland.ORCID https://orcid.org/0000-0002-6912-2458
Øyvind MolbergOslo University Hospital, Oslo, Norway.
Olivier BenvenisteSorbonne Université, AP-HP, Myology Research Center UMR974, Pitié-Salpêtrière Hospital, Paris, France.ORCID https://orcid.org/0000-0002-1167-5797
Timothy RadstakeUniversity Medical Center Utrecht, Utrecht, The Netherlands.
Andrea DoriaUniversity of Padova, Padova, Italy.ORCID https://orcid.org/0000-0003-0548-4983
Jan L De BleeckerGhent University, Ghent, Belgium.ORCID https://orcid.org/0000-0002-1328-1812
Boel De PaepeGhent University, Ghent, Belgium.ORCID https://orcid.org/0000-0001-9403-4401
Britta MaurerUniversity Hospital, Bern, Switzerland.ORCID https://orcid.org/0000-0001-9385-8097
William E OllierManchester Metropolitan University, Manchester, United Kingdom.ORCID https://orcid.org/0000-0001-6502-6584
Leonid PadyukovKarolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.ORCID https://orcid.org/0000-0003-2950-5670
Lucy R WedderburnNIHR Biomedical Research Centre at Great Ormond Street Hospital, Centre for Adolescent Rheumatology Versus Arthritis, and University College London, London, United Kingdom.ORCID https://orcid.org/0000-0002-7495-1429
Hector ChinoyNIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust and The University of Manchester, Manchester, United Kingdom, and Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust and Manchester Academic Health Science Centre, Salford, United Kingdom.ORCID https://orcid.org/0000-0001-6492-1288
Janine A LambThe University of Manchester, Manchester, United Kingdom.ORCID https://orcid.org/0000-0002-7248-0539
Christopher I AmosBaylor College of Medicine, Houston, Texas.ORCID https://orcid.org/0000-0002-8540-7023
Myositis Genetics Consortium

Funding

Translating Molecular and Clinical Data to Population Lung Cancer Risk AssessmentU19CA203654 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Christopher I. Amos · 2017 to 2026
$23.7M
Training in Precision Environmental Health SciencesT32ES027801 · NIEHS · BAYLOR COLLEGE OF MEDICINE · PI Cheryl L. Walker · 2018 to 2026
$2.8M
Medical Research Council MR/N003322/1Myositis UK 18474NCI NIH HHS U19 CA203654NIEHS NIH HHS Intramural Research ProgramNIEHS NIH HHS T32 ES027801NIHR Manchester Biomedical Research Centre NIHR203308Region Stockholm Avtal om Läkarutbildning och Forskning (ALF project)The Cure JM Foundationthe Czech Ministry of Health 00023728the King Gustaf V 80 Year FoundationThe Swedish Research Council 2020-01378the Swedish Rheumatism AssociationTraining Program fellowship T32ES027801Translational Precision Environmental Health Science (TPEHS)Versus Arthritis 20380
6 · The paper itself

Abstract

objectiveIdiopathic inflammatory myopathies (IIMs, myositis) are rare systemic autoimmune disorders that lead to muscle inflammation, weakness, and extramuscular manifestations, with a strong genetic component influencing disease development and progression. Previous genome-wide association studies identified loci associated with IIMs. In this study, we imputed data from two prior genome-wide myositis studies and analyzed the largest myositis data set to date to identify novel risk loci and susceptibility genes associated with IIMs and its clinical subtypes.

methodsWe performed association analyses on 14,903 individuals (3,206 patients and 11,697 controls) with genotypes and imputed data from the Trans-Omics for Precision Medicine reference panel. Fine-mapping and expression quantitative trait locus colocalization analyses in myositis-relevant tissues indicated potential causal variants. Functional annotation and network analyses using the random walk with restart (RWR) algorithm explored underlying genetic networks and drug repurposing opportunities.

resultsOur analyses identified novel risk loci and susceptibility genes, such as FCRLA, NFKB1, IRF4, DCAKD, and ATXN2 in overall IIMs; NEMP2 in polymyositis; ACBC11 in dermatomyositis; and PSD3 in myositis with anti-histidyl-transfer RNA synthetase autoantibodies (anti-Jo-1). We also characterized effects of HLA region variants and the role of C4. Colocalization analyses suggested putative causal variants in DCAKD in skin and muscle, HCP5 in lung, and IRF4 in Epstein-Barr virus (EBV)-transformed lymphocytes, lung, and whole blood. RWR further prioritized additional candidate genes, including APP, CD74, CIITA, NR1H4, and TXNIP, for future investigation.

conclusionOur study uncovers novel genetic regions contributing to IIMs, advancing our understanding of myositis pathogenesis and offering new insights for future research.

Indexed as

MyositisGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideQuantitative Trait Loci

Identifiers

PMID39679859
PMCPMC12124973

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.