Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

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Evangelou, Evangelos (author)

Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

Article/chapterEnglish2011

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2010-11-10
BMJ,2011

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LIBRIS-ID:oai:lup.lub.lu.se:cfe6375b-2092-449a-9442-f2791948a035
https://lup.lub.lu.se/record/1876478URI
https://doi.org/10.1136/ard.2010.132787DOI

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Language:English
Summary in:English

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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(-9)), 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.

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Valdes, Ana M. (author)
Kerkhof, Hanneke J. M. (author)
Styrkarsdottir, Unnur (author)
Zhu, YanYan (author)
Meulenbelt, Ingrid (author)
Lories, Rik J. (author)
Karassa, Fotini B. (author)
Tylzanowski, Przemko (author)
Bos, Steffan D. (author)
Akune, Toru (author)
Arden, Nigel K. (author)
Carr, Andrew (author)
Chapman, Kay (author)
Cupples, L. Adrienne (author)
Dai, Jin (author)
Deloukas, Panos (author)
Doherty, Michael (author)
Doherty, Sally (author)
Engström, GunnarLund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups(Swepub:lu)smi-gen (author)
Gonzalez, Antonio (author)
Halldorsson, Bjarni V. (author)
Hammond, Christina L. (author)
Hart, Deborah J. (author)
Helgadottir, Hafdis (author)
Hofman, Albert (author)
Ikegawa, Shiro (author)
Ingvarsson, Thorvaldur (author)
Jiang, Qing (author)
Jonsson, Helgi (author)
Kaprio, Jaakko (author)
Kawaguchi, Hiroshi (author)
Kisand, Kalle (author)
Kloppenburg, Margreet (author)
Kujala, Urho M. (author)
Lohmander, StefanLund University,Lunds universitet,Ortopedi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Orthopaedics (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)ort-slo (author)
Loughlin, John (author)
Luyten, Frank P. (author)
Mabuchi, Akihiko (author)
McCaskie, Andrew (author)
Nakajima, Masahiro (author)
Nilsson, PeterLund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups(Swepub:lu)medf-pni (author)
Nishida, Nao (author)
Ollier, William E. R. (author)
Panoutsopoulou, Kalliope (author)
van de Putte, Tom (author)
Ralston, Stuart H. (author)
Rivadeneira, Fernado (author)
Saarela, Janna (author)
Schulte-Merker, Stefan (author)
Shi, Dongquan (author)
Slagboom, P. Eline (author)
Sudo, Akihiro (author)
Tamm, Agu (author)
Tamm, Ann (author)
Thorleifsson, Gudmar (author)
Thorsteinsdottir, Unnur (author)
Tsezou, Aspasia (author)
Wallis, Gillian A. (author)
Wilkinson, J. Mark (author)
Yoshimura, Noriko (author)
Zeggini, Eleftheria (author)
Zhai, Guangju (author)
Zhang, Feng (author)
Jonsdottir, Ingileif (author)
Uitterlinden, Andre G. (author)
Felson, David T. (author)
van Meurs, Joyce B. (author)
Stefansson, Kari (author)
Ioannidis, John P. A. (author)
Spector, Timothy D. (author)
Kardiovaskulär forskning - epidemiologiForskargrupper vid Lunds universitet (creator_code:org_t)

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In:Annals of the Rheumatic Diseases: BMJ70:2, s. 349-3551468-20600003-4967

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By the author/editor: Evangelou, Evang ...; Valdes, Ana M.; Kerkhof, Hanneke ...; Styrkarsdottir, ...; Zhu, YanYan; Meulenbelt, Ingr ...; show more...; Lories, Rik J.; Karassa, Fotini ...; Tylzanowski, Prz ...; Bos, Steffan D.; Akune, Toru; Arden, Nigel K.; Carr, Andrew; Chapman, Kay; Cupples, L. Adri ...; Dai, Jin; Deloukas, Panos; Doherty, Michael; Doherty, Sally; Engström, Gunnar; Gonzalez, Antoni ...; Halldorsson, Bja ...; Hammond, Christi ...; Hart, Deborah J.; Helgadottir, Haf ...; Hofman, Albert; Ikegawa, Shiro; Ingvarsson, Thor ...; Jiang, Qing; Jonsson, Helgi; Kaprio, Jaakko; Kawaguchi, Hiros ...; Kisand, Kalle; Kloppenburg, Mar ...; Kujala, Urho M.; Lohmander, Stefa ...; Loughlin, John; Luyten, Frank P.; Mabuchi, Akihiko; McCaskie, Andrew; Nakajima, Masahi ...; Nilsson, Peter; Nishida, Nao; Ollier, William ...; Panoutsopoulou, ...; van de Putte, To ...; Ralston, Stuart ...; Rivadeneira, Fer ...; Saarela, Janna; Schulte-Merker, ...; Shi, Dongquan; Slagboom, P. Eli ...; Sudo, Akihiro; Tamm, Agu; Tamm, Ann; Thorleifsson, Gu ...; Thorsteinsdottir ...; Tsezou, Aspasia; Wallis, Gillian ...; Wilkinson, J. Ma ...; Yoshimura, Norik ...; Zeggini, Elefthe ...; Zhai, Guangju; Zhang, Feng; Jonsdottir, Ingi ...; Uitterlinden, An ...; Felson, David T.; van Meurs, Joyce ...; Stefansson, Kari; Ioannidis, John ...; Spector, Timothy ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Rheumatology and ...

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