Advanced

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

Evangelou, Evangelos; Valdes, Ana M.; Kerkhof, Hanneke J. M.; Styrkarsdottir, Unnur; Zhu, YanYan; Meulenbelt, Ingrid; Lories, Rik J.; Karassa, Fotini B.; Tylzanowski, Przemko and Bos, Steffan D., et al. (2011) In Annals of the Rheumatic Diseases 70(2). p.349-355
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of the Rheumatic Diseases
volume
70
issue
2
pages
349 - 355
publisher
British Medical Association
external identifiers
  • wos:000286179000022
  • scopus:78751703383
ISSN
1468-2060
DOI
10.1136/ard.2010.132787
language
English
LU publication?
yes
id
cfe6375b-2092-449a-9442-f2791948a035 (old id 1876478)
date added to LUP
2011-04-01 11:26:52
date last changed
2017-11-12 03:36:51
@article{cfe6375b-2092-449a-9442-f2791948a035,
  abstract     = {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.},
  author       = {Evangelou, Evangelos and Valdes, Ana M. and Kerkhof, Hanneke J. M. and Styrkarsdottir, Unnur and Zhu, YanYan and Meulenbelt, Ingrid and Lories, Rik J. and Karassa, Fotini B. and Tylzanowski, Przemko and Bos, Steffan D. and Akune, Toru and Arden, Nigel K. and Carr, Andrew and Chapman, Kay and Cupples, L. Adrienne and Dai, Jin and Deloukas, Panos and Doherty, Michael and Doherty, Sally and Engström, Gunnar and Gonzalez, Antonio and Halldorsson, Bjarni V. and Hammond, Christina L. and Hart, Deborah J. and Helgadottir, Hafdis and Hofman, Albert and Ikegawa, Shiro and Ingvarsson, Thorvaldur and Jiang, Qing and Jonsson, Helgi and Kaprio, Jaakko and Kawaguchi, Hiroshi and Kisand, Kalle and Kloppenburg, Margreet and Kujala, Urho M. and Lohmander, Stefan and Loughlin, John and Luyten, Frank P. and Mabuchi, Akihiko and McCaskie, Andrew and Nakajima, Masahiro and Nilsson, Peter and Nishida, Nao and Ollier, William E. R. and Panoutsopoulou, Kalliope and van de Putte, Tom and Ralston, Stuart H. and Rivadeneira, Fernado and Saarela, Janna and Schulte-Merker, Stefan and Shi, Dongquan and Slagboom, P. Eline and Sudo, Akihiro and Tamm, Agu and Tamm, Ann and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Tsezou, Aspasia and Wallis, Gillian A. and Wilkinson, J. Mark and Yoshimura, Noriko and Zeggini, Eleftheria and Zhai, Guangju and Zhang, Feng and Jonsdottir, Ingileif and Uitterlinden, Andre G. and Felson, David T. and van Meurs, Joyce B. and Stefansson, Kari and Ioannidis, John P. A. and Spector, Timothy D.},
  issn         = {1468-2060},
  language     = {eng},
  number       = {2},
  pages        = {349--355},
  publisher    = {British Medical Association},
  series       = {Annals of the Rheumatic Diseases},
  title        = {Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22},
  url          = {http://dx.doi.org/10.1136/ard.2010.132787},
  volume       = {70},
  year         = {2011},
}