Evidence map›Paper›PMID 38734017›Full record

SynthesisThe Lancet. Rheumatology2024

Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study.

Gonzalo Borrego-Yaniz, Lourdes Ortiz-Fernández, Adela Madrid-Paredes, Martin Kerick, José Hernández-Rodríguez, Sarah L Mackie, Augusto Vaglio, Santos Castañeda, Roser Solans, Jaume Mestre-Torres and 44 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in The Lancet. Rheumatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 2 pooled it
–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

10 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  10. Neutrophil extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

54 authors.

Gonzalo Borrego-YanizInstitute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
Lourdes Ortiz-FernándezInstitute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
Adela Madrid-ParedesInstitute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain; Department of Clinical Pharmacy, San Cecilio University Hospital, Instituto de Investigación Biosanitaria de Granada (ibs.Granada), Granada, Spain.
Martin KerickInstitute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
José Hernández-RodríguezVasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Sarah L MackieSchool of Medicine, University of Leeds, Leeds, UK; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Augusto VaglioDepartment of Biomedical Experimental and Clinical Sciences "Mario Serio", University of Florence, Florence, Italy; Meyer Children's Hospital, Nephrology and Dialysis Unit, Florence, Italy.
Santos CastañedaDepartment of Rheumatology, Hospital de la Princesa, IIS-IP, Madrid, Spain.
Roser SolansAutoimmune Systemic Diseases Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
Jaume Mestre-TorresAutoimmune Systemic Diseases Unit, Department of Internal Medicine, Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.
Nader KhalidiDivision of Rheumatology, McMaster University, Hamilton, ON, Canada.
Carol A LangfordDepartment of Rheumatic and Immunologic Diseases, Cleveland Clinic, Cleveland, OH, USA.
Steven YtterbergDivision of Rheumatology, Mayo Clinic, Rochester, NY, USA.
Lorenzo BerettaReferral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
Marcello GovoniDepartment of Rheumatology, Azienda Ospedaliero Universitaria S Anna, University of Ferrara, Ferrara, Italy.
Giacomo EmmiDepartment of Experimental and Clinical Medicine, University of Firenze, Florence, Italy; Centre for Inflammatory Diseases, Department of Medicine, Monash Medical Centre, Monash University, Clayton, VIC, Australia.
Marco A CimminoResearch Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy.
Torsten WitteHannover Medical School, Hannover, Germany.
Thomas NeumannKlinik für Innere Medizin III, University-Hospital Jena, Jena, Germany; Department of Rheumatology, Cantonal Hospital St Gallen, St Gallen, Switzerland.
Julia HolleVasculitis Clinic, Klinikum Bad Bramstedt and University Hospital of Schleswig Holstein, Bad Bramstedt, Germany.
Verena SchönauDepartment of Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany.
Gregory PugnetDepartment of Internal Medicine, Toulouse University Hospital Center, Toulouse, France.
Thomas PapoHôpital Bichat, Université Paris-Cité, Service de Médecine Interne, Paris, France.
Julien HarocheDepartment of Internal Medicine and French Reference Center for Rare Auto-immune & Systemic Diseases, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
Alfred MahrECSTRRA Research Unit, Centre of Research in Epidemiology and Statistics, Sorbonne Paris Cité Research Center UMR 1153, Inserm, Paris, France.
Luc MouthonCochin Hospital, National Referral Center for Rare Autoimmune and Systemic Diseases, Université Paris Descartes, Department of Internal Medicine, Assistance Publique-Hôpitaux de Paris, Paris, France.
Øyvind MolbergDepartment of Rheumatology, Oslo University Hospital, Oslo, Norway.
Andreas P DiamantopoulosDepartment of Rheumatology, Hospital of Southern Norway Trust, Kristiansand, Norway.
Alexandre VoskuylDepartment of Rheumatology and Clinical Immunology, Amsterdam University Medical Centre, Amsterdam, Netherlands.
Thomas DaikelerDepartment of Rheumatology, University Hospital Basel and Department of Clinical Research, University of Basel, Basel, Switzerland.
Christoph T BergerDepartment of Biomedicine and Department of Internal Medicine, Translational Immunology and Medical Outpatient Clinic, University Hospital Basel, Basel, Switzerland.
Eamonn S MolloyDepartment of Rheumatology, Centre for Arthritis and Rheumatic Diseases, St Vincent's University Hospital, Dublin Academic Medical Centre, Dublin, Ireland.
Daniel BlockmansDepartment of General Internal Medicine, University Hospital Gasthuisberg, Leuven, Belgium.
Yannick van SleenDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Mark IlesSchool of Medicine, University of Leeds, Leeds, UK; Leeds Institute for Data Analytics, University of Leeds, Leeds, UK; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Louise SorensenSchool of Medicine, University of Leeds, Leeds, UK; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK; NIHR Leeds Medtech and In Vitro Diagnostics Co-Operative, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Raashid LuqmaniNuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences, Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.
Gary ReynoldsCenter for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.
Marwan BukhariRheumatology Department, University Hospitals of Morecambe Bay NHS Foundation Trust, Royal Lancaster Infirmary, Lancaster, UK; Faculty of Health and Medicine, Lancaster University, Lancaster, UK.
Shweta BhagatWest Suffolk NHS Foundation Trust, Bury Saint Edmunds, Bury St Edmunds, UK.
Norberto Ortego-CentenoDepartment of Medicine, University of Granada, Instituto de Investigación Biosanitaria de Granada ibs GRANADA, Granada, Spain.
Elisabeth BrouwerDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Peter LamprechtDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
Sebastian KlapaDepartment of Rheumatology and Clinical Immunology, University of Lübeck, Lübeck, Germany.
Carlo SalvaraniAzienda USL-IRCCS di Reggio Emilia and Università di Modena e Reggio Emilia, Reggio Emilia, Italy.
Peter A MerkelDivision of Rheumatology, Department of Medicine, and Division of Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
María C CidVasculitis Research Unit, Department of Autoimmune Diseases, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Miguel A González-GayDivision of Rheumatology, IIS-Fundación Jiménez Díaz, Madrid, Spain; Department of Medicine, University of Cantabria, Santander, Spain.
Ann W MorganSchool of Medicine, University of Leeds, Leeds, UK; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK; NIHR Leeds Medtech and In Vitro Diagnostics Co-Operative, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
Javier MartinInstitute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain.
Ana MárquezInstitute of Parasitology and Biomedicine López-Neyra, Consejo Superior de Investigaciones Científicas (CSIC), Granada, Spain. Electronic address: anamaort@ipb.csic.es.
Spanish GCA Group
UK GCA Consortium
Vasculitis Clinical Research Consortium

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGiant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci.

methodsWe collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings.

findingsWe included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10

interpretationWe have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis.

fundingInstitute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Research.

Indexed as

Genetic Predisposition to DiseaseGenome-Wide Association StudyGiant Cell ArteritisAgedCase-Control StudiesFemaleGenetic LociHumansMaleMiddle AgedPolymorphism, Single Nucleotide

Identifiers

PMID38734017
PMCPMC11108802

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.