Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23989986
TITLE
A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip.
ABSTRACT
OBJECTIVES NlmCategory: OBJECTIVE
Osteoarthritis (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.
METHODS NlmCategory: METHODS
We 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.
RESULTS NlmCategory: RESULTS
We 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).
CONCLUSIONS NlmCategory: CONCLUSIONS
Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
DATE PUBLISHED
2014 Dec
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2013/08/29
entrez 2013/08/31 06:00
pubmed 2013/08/31 06:00
medline 2014/12/31 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Evangelou E Evangelou Evangelos E Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Kerkhof HJ Kerkhof Hanneke J HJ Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Styrkarsdottir U Styrkarsdottir Unnur U Department of Population Genetics, deCODE Genetics, Reykjavik, Iceland.
Ntzani EE Ntzani Evangelia E EE Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
Bos SD Bos Steffan D SD Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands Netherlands Consortium for Healthy Ageing, The Netherlands.
Esko T Esko Tonu T Estonian Genome Center, University of Tartu, Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Evans DS Evans Daniel S DS California Pacific Medical Center Research Institute, San Francisco, USA.
Metrustry S Metrustry Sarah S Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
Panoutsopoulou K Panoutsopoulou Kalliope K Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Ramos YF Ramos Yolande F M YF Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Thorleifsson G Thorleifsson Gudmar G Department of Population Genetics, deCODE Genetics, Reykjavik, Iceland.
Tsilidis KK Tsilidis Konstantinos K KK Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
arcOGEN Consortium
Arden N Arden Nigel N NIHR 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.
Aslam N Aslam Nadim N Worcestershire Royal Hospital, Worcestershire Acute Hospitals NHS Trust, Worcester, UK.
Bellamy N Bellamy Nicholas N Centre of National Research on Disability and Rehabilitation Medicine, The University of Queensland, Brisbane, Australia.
Birrell F Birrell Fraser F Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK Wansbeck General Hospital, Northumbria Healthcare NHS Foundation Trust, Ashington, UK.
Blanco FJ Blanco Francisco J FJ Rheumatology Division, Instituto de Investigación Biomédica-Hospital Universitario A Coruña, A Corunna, Spain.
Carr A Carr Andrew A NIHR Biomedical Research Unit and ARUK Centre of excellence for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, UK.
Chapman K Chapman Kay K NIHR Biomedical Research Unit and ARUK Centre of excellence for Sport, Exercise and Osteoarthritis, University of Oxford, Oxford, UK.
Day-Williams AG Day-Williams Aaron G AG Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Deloukas P Deloukas Panos P Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Doherty M Doherty Michael M Department of Academic Rheumatology, University of Nottingham, Nottingham, UK.
Engström G Engström Gunnar G Department of Clinical Sciences Malmo, Lund University, Malmo, Sweden.
Helgadottir HT Helgadottir Hafdis T HT Department of Population Genetics, deCODE Genetics, Reykjavik, Iceland.
Hofman A Hofman Albert A Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Ingvarsson T Ingvarsson Thorvaldur T Department of Orthopedic Surgery, Akureyri Hospital, Akureyri, Iceland School of Health Sciences, University of Akureyri, Akureyri, Iceland.
Jonsson H Jonsson Helgi H Department of Medicine, The National University Hospital of Iceland, Reykjavik, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Keis A Keis Aime A Department of Public Health, University of Tartu, Tartu, Estonia Orthopedic Surgeons, Elva Hospital, Elva, Estonia.
Keurentjes JC Keurentjes J Christiaan JC Department of Orthopedics, Leiden University Medical Center, Leiden, The Netherlands.
Kloppenburg M Kloppenburg Margreet M Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
Lind PA Lind Penelope A PA Department of Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
McCaskie A McCaskie Andrew A Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Martin NG Martin Nicholas G NG Department of Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Milani L Milani Lili L Estonian Genome Center, University of Tartu, Tartu, Estonia.
Montgomery GW Montgomery Grant W GW Department of Molecular Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Nelissen RG Nelissen Rob G H H RG Department of Orthopedics, Leiden University Medical Center, Leiden, The Netherlands.
Nevitt MC Nevitt Michael C MC Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
Nilsson PM Nilsson Peter M PM Department of Clinical Sciences Malmo, Lund University, Malmo, Sweden.
Ollier WE Ollier William Er WE Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
Parimi N Parimi Neeta N California Pacific Medical Center Research Institute, San Francisco, USA.
Rai A Rai Ashok A Worcestershire Acute Hospitals NHS Trust, Worcester, UK.
Ralston SH Ralston Stuart H SH Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Reed MR Reed Mike R MR Wansbeck General Hospital, Northumbria Healthcare NHS Foundation Trust, Ashington, UK.
Riancho JA Riancho Jose A JA Department of Internal Medicine, Hospital U.M. Valdecilla-IFIMAV, University of Cantabria, Santander, Spain.
Rivadeneira F Rivadeneira Fernando F Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Rodriguez-Fontenla C Rodriguez-Fontenla Cristina C Laboratorio Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
Southam L Southam Lorraine L Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Thorsteinsdottir U Thorsteinsdottir Unnur U Department of Population Genetics, deCODE Genetics, Reykjavik, Iceland Department of Medicine, The National University Hospital of Iceland, Reykjavik, Iceland.
Tsezou A Tsezou Aspasia A Department of Biology, University of Thessaly, Medical School, Larissa, Greece.
Wallis GA Wallis Gillian A GA Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK.
Wilkinson JM Wilkinson J Mark JM Department of Human Metabolism, University of Sheffield, Sheffield, UK.
Gonzalez A Gonzalez Antonio A Laboratorio Investigacion 10 and Rheumatology Unit, Instituto de Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Santiago de Compostela, Spain.
Lane NE Lane Nancy E NE Department of Medicine, University of California at Davis, Sacramento, USA.
Lohmander LS Lohmander L Stefan LS Research 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.
Loughlin J Loughlin John J Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Tartu, Estonia Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Uitterlinden AG Uitterlinden Andre G AG Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Jonsdottir I Jonsdottir Ingileif I Department of Population Genetics, deCODE Genetics, Reykjavik, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Stefansson K Stefansson Kari K Department of Population Genetics, deCODE Genetics, Reykjavik, Iceland Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Slagboom PE Slagboom P Eline PE Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands Netherlands Consortium for Healthy Ageing, The Netherlands.
Zeggini E Zeggini Eleftheria E Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, UK.
Meulenbelt I Meulenbelt Ingrid I Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands Netherlands Consortium for Healthy Ageing, The Netherlands.
Ioannidis JP Ioannidis John Pa JP Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, USA.
Spector TD Spector Tim D TD Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
van Meurs JB van Meurs Joyce B J JB Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Valdes AM Valdes Ana M AM Department of Twin Research & Genetic Epidemiology, King's College London, London, UK Department of Academic Rheumatology, University of Nottingham, Nottingham, UK.
INVESTIGATORS
JOURNAL
VOLUME: 73
ISSUE: 12
TITLE: Annals of the rheumatic diseases
ISOABBREVIATION: Ann. Rheum. Dis.
YEAR: 2014
MONTH: Dec
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1468-2060
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Ann Rheum Dis
COUNTRY: England
ISSNLINKING: 0003-4967
NLMUNIQUEID: 0372355
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Nature. 2012 Nov 1;491(7422):56-65 23128226
Cites Lancet. 2012 Sep 1;380(9844):815-23 22763110
Cites Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6379-84 10823921
Cites Arthritis Rheum. 2003 Feb;48(2):391-5 12571848
Cites BMJ. 2003 Sep 6;327(7414):557-60 12958120
Cites Osteoarthritis Cartilage. 2004;12 Suppl A:S39-44 14698640
Cites J Biol Chem. 2004 Jul 23;279(30):31105-12 15145939
Cites Science. 1994 Jun 3;264(5164):1415-21 8197455
Cites Biorheology. 2006;43(3-4):223-33 16912396
Cites Osteoarthritis Cartilage. 2006 Oct;14(10):991-1001 16682236
Cites Nucleic Acids Res. 2006;34(19):e128 17012270
Cites Osteoarthritis Cartilage. 2007 Feb;15(2):120-7 17113325
Cites Nat Genet. 2007 Jul;39(7):906-13 17572673
Cites Arthritis Rheum. 2007 Jul;56(7):2322-34 17599752
Cites Nature. 2007 Oct 18;449(7164):851-61 17943122
Cites Arthritis Rheum. 2008 Jan;58(1):26-35 18163497
Cites Hum Mol Genet. 2008 Jun 15;17(12):1867-75 18334578
Cites Curr Opin Rheumatol. 2008 Sep;20(5):553-9 18698177
Cites Med Clin North Am. 2009 Jan;93(1):45-66, x 19059021
Cites Arthritis Rheum. 2010 Feb;62(2):499-510 20112360
Cites Nat Methods. 2010 Apr;7(4):248-9 20354512
Cites Nature. 2010 Oct 14;467(7317):832-8 20881960
Cites Nat Genet. 2010 Nov;42(11):937-48 20935630
Cites Ann N Y Acad Sci. 2010 Nov;1211:37-50 21062294
Cites Ann Rheum Dis. 2011 Jan;70(1):164-7 20724312
Cites Nat Rev Rheumatol. 2011 Jan;7(1):23-32 21079645
Cites Ann Rheum Dis. 2011 Feb;70(2):349-55 21068099
Cites J Biol Chem. 2011 Feb 18;286(7):5691-707 21127072
Cites Osteoarthritis Cartilage. 2011 Mar;19(3):254-64 21059398
Cites Ann Rheum Dis. 2011 May;70(5):873-5 20870806
Cites Am J Hum Genet. 2011 May 13;88(5):586-98 21565292
Cites Am J Hum Genet. 2011 Sep 9;89(3):446-50 21871595
Cites J Endocrinol. 2012 Jun;213(3):209-21 22454529
Cites Proc Natl Acad Sci U S A. 2012 May 22;109(21):8218-23 22566624
Cites Ann Rheum Dis. 2013 Jul;72(7):1264-5 23505243
GRANTS
GRANTID AGENCY COUNTRY
G0800803 Medical Research Council United Kingdom
P50 AR060752 NIAMS NIH HHS United States
R01 AG005407 NIA NIH HHS United States
R01 AR052000 NIAMS NIH HHS United States
U01 AR066160 NIAMS NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
Epidemiology
Gene Polymorphism
Osteoarthritis
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Calcium-Calmodulin-Dependent Protein Kinase Type 2 genetics
European Continental Ancestry Group genetics
Female genetics
Gene Frequency genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
HMGN Proteins genetics
Homeodomain Proteins genetics
Humans genetics
Immediate-Early Proteins genetics
Male genetics
Nuclear Receptor Coactivator 3 genetics
Osteoarthritis, Hip genetics
Polymorphism, Single Nucleotide genetics
Protein-Serine-Threonine Kinases genetics
Protein-Tyrosine Kinases genetics
Sex Factors genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 HMGN Proteins
0 HMGN3 protein, human
0 Homeodomain Proteins
0 IFRD1 protein, human
0 Immediate-Early Proteins
0 PHF2 protein, human
EC 2.3.1.48 NCOA3 protein, human
EC 2.3.1.48 Nuclear Receptor Coactivator 3
EC 2.7.1.- Dyrk kinase
EC 2.7.10.1 Protein-Tyrosine Kinases
EC 2.7.11.1 Protein-Serine-Threonine Kinases
EC 2.7.11.17 CAMK2B protein, human
EC 2.7.11.17 Calcium-Calmodulin-Dependent Protein Kinase Type 2
OTHER ID's
OTHERID SOURCE
PMC4251181 NLM