SynthesisAnnals of the rheumatic diseases2014
A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip.
Open access · hybridAbstract readMeta-AnalysisReview
In one paragraph
Synthesis in Annals of the rheumatic diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 10 of them syntheses that pooled it.
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64citing papers in PubMed, 10 pooled it
10.6field-weighted citation impact, top 1% of its field
What it found
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The trial behind it
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Who cites it
64 citing papers in PubMed, 10 syntheses or guidelines pooled it, 128 citations in OpenAlex.
- Associations between adipokines gene polymorphisms and knee osteoarthritis: a meta-analysis.BMC musculoskeletal disorders · 2022Pooled it
- Mitochondrial DNA variants and pulmonary function in older persons.Experimental gerontology · 2019Pooled it
- Meta-analysis identifies mitochondrial DNA sequence variants associated with walking speed.GeroScience · 2018Pooled it
- Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis.Nature genetics · 2018Pooled it
- Genome-wide meta-analysis of 158,000 individuals of European ancestry identifies three loci associated with chronic back pain.PLoS genetics · 2018Pooled it
- Association between Fas/FasL gene polymorphism and musculoskeletal degenerative diseases: a meta-analysis.BMC musculoskeletal disorders · 2018Pooled it
- Pooled it
- Genome-wide association and functional studies identify a role for IGFBP3 in hip osteoarthritis.Annals of the rheumatic diseases · 2015Pooled it
- Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss.Human molecular genetics · 2015Pooled it
- Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31.Nature genetics · 2014Pooled it
- Monoallelic Gene Expression: Stochastic or Clonal? From Detection to Mechanisms and Clinical Significance.International journal of molecular sciences · 2026Review
- Association of single nucleotide polymorphisms in FILIP1-SENP6 and FTO with temporomandibular joint osteoarthritis: clinical and in silico study.Scientific reports · 2026Article
- Genomic Determinants of Knee Joint Biomechanics: An Exploration into the Molecular Basis of Locomotor Function, a Narrative Review.Current issues in molecular biology · 2024Review
- Causal link between metabolic related factors and osteoarthritis: a Mendelian randomization investigation.Frontiers in nutrition · 2024Article
- Maternal pre-pregnancy BMI, offspring epigenome-wide DNA methylation, and childhood obesity: findings from the Boston Birth Cohort.BMC medicine · 2023Article
- The Physiological Functions and Polymorphisms of Type II Deiodinase.Endocrinology and metabolism (Seoul, Korea) · 2023Review
- Genetics of osteoarthritis.Osteoarthritis and cartilage · 2022Review
- Wear patterns in knee OA correlate with native limb geometry.Frontiers in bioengineering and biotechnology · 2022Article
- Inhibition of nuclear receptor RORα attenuates cartilage damage in osteoarthritis by modulating IL-6/STAT3 pathway.Cell death & disease · 2021Article
- The Genetic Epidemiology of Joint Shape and the Development of Osteoarthritis.Calcified tissue international · 2021Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
67 authors at 20 institutions in 10 countries.
Evangelos EvangelouDepartment of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Hanneke J KerkhofDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Unnur StyrkarsdottirDepartment of Population Genetics, deCODE Genetics, Reykjavik, Iceland.
Evangelia E NtzaniDepartment of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
Steffan D BosDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands Netherlands Consortium for Healthy Ageing, The Netherlands.
Tonu EskoEstonian Genome Center, University of Tartu, Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Daniel S EvansCalifornia Pacific Medical Center Research Institute, San Francisco, USA.
Sarah MetrustryDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Kalliope PanoutsopoulouDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Yolande F M RamosDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Gudmar ThorleifssonDepartment of Population Genetics, deCODE Genetics, Reykjavik, Iceland.
Konstantinos K TsilidisDepartment of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
arcOGEN Consortium
Nigel ArdenNIHR Biomedical Research Unit and ARUK Centre of excellence for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, UK MRC Epidemiology Resource Centre, University of Southampton, Southampton, UK.
Nadim AslamWorcestershire Royal Hospital, Worcestershire Acute Hospitals NHS Trust, Worcester, UK.
Nicholas BellamyCentre of National Research on Disability and Rehabilitation Medicine, The University of Queensland, Brisbane, Australia.
Fraser BirrellMusculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK Wansbeck General Hospital, Northumbria Healthcare NHS Foundation Trust, Ashington, UK.
Francisco J BlancoRheumatology Division, Instituto de Investigación Biomédica-Hospital Universitario A Coruña, A Corunna, Spain.
Andrew CarrNIHR Biomedical Research Unit and ARUK Centre of excellence for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, UK.
Kay ChapmanNIHR Biomedical Research Unit and ARUK Centre of excellence for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, UK.
Aaron G Day-WilliamsDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Panos DeloukasDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Michael DohertyDepartment of Academic Rheumatology, University of Nottingham, Nottingham, UK.
Gunnar EngströmDepartment of Clinical Sciences Malmo, Lund University, Malmo, Sweden.
Hafdis T HelgadottirDepartment of Population Genetics, deCODE Genetics, Reykjavik, Iceland.
Albert HofmanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Thorvaldur IngvarssonDepartment of Orthopedic Surgery, Akureyri Hospital, Akureyri, Iceland School of Health Sciences, University of Akureyri, Akureyri, Iceland.
Helgi JonssonDepartment of Medicine, The National University Hospital of Iceland, Reykjavik, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Aime KeisDepartment of Public Health, University of Tartu, Tartu, Estonia Orthopedic Surgeons, Elva Hospital, Elva, Estonia.
J Christiaan KeurentjesDepartment of Orthopedics, Leiden University Medical Center, Leiden, The Netherlands.
Margreet KloppenburgDepartment of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Penelope A LindDepartment of Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Andrew McCaskieMusculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Nicholas G MartinDepartment of Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Lili MilaniEstonian Genome Center, University of Tartu, Tartu, Estonia.
Grant W MontgomeryDepartment of Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Rob G H H NelissenDepartment of Orthopedics, Leiden University Medical Center, Leiden, The Netherlands.
Michael C NevittDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Peter M NilssonDepartment of Clinical Sciences Malmo, Lund University, Malmo, Sweden.
William Er OllierCentre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
Neeta ParimiCalifornia Pacific Medical Center Research Institute, San Francisco, USA.
Ashok RaiWorcestershire Acute Hospitals NHS Trust, Worcester, UK.
Stuart H RalstonInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Mike R ReedWansbeck General Hospital, Northumbria Healthcare NHS Foundation Trust, Ashington, UK.
Jose A RianchoDepartment of Internal Medicine, Hospital U.M. Valdecilla-IFIMAV, University of Cantabria, Santander, Spain.
Fernando RivadeneiraDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Cristina Rodriguez-FontenlaLaboratorio Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
Lorraine SouthamDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Unnur ThorsteinsdottirDepartment of Population Genetics, deCODE Genetics, Reykjavik, Iceland Department of Medicine, The National University Hospital of Iceland, Reykjavik, Iceland.
Aspasia TsezouDepartment of Biology, University of Thessaly, Medical School, Larissa, Greece.
Gillian A WallisWellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK.
J Mark WilkinsonDepartment of Human Metabolism, University of Sheffield, Sheffield, UK.
Antonio GonzalezLaboratorio Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
Nancy E LaneDepartment of Medicine, University of California at Davis, Sacramento, USA.
L Stefan LohmanderResearch Unit for Musculoskeletal Function and Physiotherapy, and Department of Orthopedics and Traumatology, University of Southern Denmark, Odense, Denmark Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
John LoughlinMusculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Andres MetspaluEstonian Genome Center, University of Tartu, Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Andre G UitterlindenDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Ingileif JonsdottirDepartment of Population Genetics, deCODE Genetics, Reykjavik, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Kari StefanssonDepartment of Population Genetics, deCODE Genetics, Reykjavik, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
P Eline SlagboomDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands Netherlands Consortium for Healthy Ageing, The Netherlands.
Eleftheria ZegginiDepartment of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Ingrid MeulenbeltDepartment of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands Netherlands Consortium for Healthy Ageing, The Netherlands.
John Pa IoannidisDepartment of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, USA.
Tim D SpectorDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Joyce B J van MeursDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Ana M ValdesDepartment of Twin Research & Genetic Epidemiology, King's College London, London, UK Department of Academic Rheumatology, University of Nottingham, Nottingham, UK.
Leiden University Medical Center · NLErasmus MC · NLWellcome Sanger Institute · GBdeCODE Genetics (Iceland) · ISUniversity of Tartu · EEKing's College London · GBQIMR Berghofer Medical Research Institute · AUUniversity of Ioannina · GRUniversity of Oxford · GBCalifornia Pacific Medical Center · USInstituto de Investigación Sanitaria de Santiago · ESLund University · SENewcastle University · GBUniversity of Iceland · ISAkureyri Hospital · ISInstituto de Investigación Biomédica de A Coruña · ESMarqués de Valdecilla University Hospital · ESNational University Hospital of Iceland · ISNetherlands Consortium for Healthy Ageing · NLNorthumbria Healthcare NHS Foundation Trust · GB
Funding
Study of Osteoporotic FracturesR01AG005407 · NIA · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI CUMMINGS, STEVEN RON, YAFFE, KRISTINE · 1986 to 2016
$23.2MOsteoporotic Fractures in Men (MrOS) - San Francisco Coordinating CenterU01AR066160 · NIAMS · CALIFORNIA PACIFIC MED CTR RES INSTITUTE · PI CUMMINGS, STEVEN RON · 2013 to 2017
$9.3MTranslation of Quantitative Imaging in OsteoarthritisP50AR060752 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SOUZA, RICHARD BRIAN · 2011 to 2015
$6.2MThe Epidemiology and Genetics of Hip OA in Elderly MenR01AR052000 · NIAMS · UNIVERSITY OF CALIFORNIA DAVIS · PI LANE, NANCY E · 2005 to 2009
$2.5MMedical Research Council G0800803NIAMS NIH HHS P50 AR060752NIAMS NIH HHS R01 AR052000NIAMS NIH HHS U01 AR066160NIA NIH HHS R01 AG005407
Abstract
objectivesOsteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects.
methodsWe performed a two-stage meta-analysis on more than 78,000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used.
resultsWe accumulated 11,277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis).
conclusionsNovel genetic loci for hip OA were found in this meta-analysis of GWAS.
Indexed as
Calcium-Calmodulin-Dependent Protein Kinase Type 2Dyrk KinasesFemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHMGN ProteinsHomeodomain ProteinsHumansImmediate-Early ProteinsMaleNuclear Receptor Coactivator 3Osteoarthritis, HipPolymorphism, Single NucleotideProtein Serine-Threonine KinasesProtein-Tyrosine KinasesCalcium-Calmodulin-Dependent Protein Kinase Type 2CAMK2B protein, humanDyrk KinasesHMGN3 protein, humanHMGN ProteinsHomeodomain ProteinsIFRD1 protein, humanImmediate-Early ProteinsNCOA3 protein, humanNuclear Receptor Coactivator 3PHF2 protein, humanProtein Serine-Threonine KinasesProtein-Tyrosine KinasesEpidemiologyGene PolymorphismOsteoarthritis
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