Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
| Autor: | Kalle Kisand, Przemko Tylzanowski, John Loughlin, Andrew McCaskie, Nigel K Arden, Andrew Carr, Nao Nishida, Panos Deloukas, Qing Jiang, Stefan Schulte-Merker, Joyce B. J. van Meurs, Feng Zhang, Hafdis T. Helgadottir, Gunnar Engström, Toru Akune, Frank P. Luyten, Shiro Ikegawa, Fotini B. Karassa, L Stefan Lohmander, Bjarni V. Halldorsson, P. Eline Slagboom, William Ollier, Deborah J. Hart, Helgi Jonsson, Tim D. Spector, Peter M. Nilsson, John P. A. Ioannidis, Jin Dai, Guangju Zhai, Ingileif Jonsdottir, Stuart H. Ralston, Akihiro Sudo, David T. Felson, André G. Uitterlinden, Steffan D. Bos, Masahiro Nakajima, F. Rivadeneira, Antonio Gonzalez, Eleftheria Zeggini, Margreet Kloppenburg, Gillian A. Wallis, Sally A Doherty, Ana M. Valdes, Jaakko Kaprio, Agu Tamm, Kari Stefansson, Dongquan Shi, Michael Doherty, Aspasia Tsezou, L. Adrienne Cupples, Gudmar Thorleifsson, Kalliope Panoutsopoulou, Evangelos Evangelou, Albert Hofman, Ann Tamm, Unnur Thorsteinsdottir, Unnur Styrkarsdottir, Rik Lories, Urho M. Kujala, J. Mark Wilkinson, Noriko Yoshimura, Ingrid Meulenbelt, Tom Van de Putte, Janna Saarela, Akihiko Mabuchi, Thorvaldur Ingvarsson, Hanneke J. M. Kerkhof, Christina L. Hammond, Hiroshi Kawaguchi, Kay Chapman, Yanyan Zhu |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research, Cell biology, Epidemiology, Internal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Linkage disequilibrium Arthritis Genome-wide association study Osteoarthritis Osteoarthritis Knee/*genetics 0302 clinical medicine Immunology and Allergy HETEROGENEITY Genetics Aged 80 and over 0303 health sciences JOINT GDF5 Osteoarthritis Knee Middle Aged 3. Good health Phenotype OBESITY Female Chromosomes Human Pair 7 Adult Genotype Immunology risk-factors body-mass gdf5 hip classification heterogeneity obesity cohorts joint frzb Locus (genetics) Biology Polymorphism Single Nucleotide General Biochemistry Genetics and Molecular Biology Article CLASSIFICATION FRZB 03 medical and health sciences Young Adult Rheumatology medicine Humans Genetic Predisposition to Disease Gene 030304 developmental biology Genetic association Aged 030203 arthritis & rheumatology HIP Gene Expression Profiling Chromosomes Human Pair 7/*genetics COHORTS medicine.disease BODY-MASS Gene expression profiling RISK-FACTORS Gene Expression Profiling/methods Genome-Wide Association Study |
| Zdroj: | Annals of the Rheumatic Diseases, 70(2), 349-355. BMJ PUBLISHING GROUP Annals of the Rheumatic Diseases, 70(2), 349-355. BMJ Publishing Group Annals of the Rheumatic Diseases Annals of the Rheumatic Diseases; Vol 70 Annals of the Rheumatic Diseases, 70(2), 349-355 |
| ISSN: | 0003-4967 |
| DOI: | 10.1136/ard.2010.132787 |
| Popis: | OBJECTIVES: Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. METHODS: A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. RESULTS: With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p=9.2 x 10), thereby confirming its role as a susceptibility locus for OA. CONCLUSION: The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment. [KEYWORDS: Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 7/ genetics, Female, Gene Expression Profiling/methods, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Osteoarthritis, Knee/ genetics, Phenotype, Polymorphism, Single Nucleotide, Young Adult] |
| Databáze: | OpenAIRE |
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