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

Evangelos Evangelou; Ana M. Valdes; Hanneke J. M. Kerkhof; Unnur Styrkarsdottir; YanYan Zhu; Ingrid Meulenbelt; Rik J. Lories; Fotini B. Karassa; Przemko Tylzanowski; Steffan D. Bos; Toru Akune; Nigel K. Arden; Andrew Carr; Kay Chapman; L. Adrienne Cupples; Jin Dai; Panos Deloukas; Michael Doherty; Sally Doherty; Gunnar Engstrom; Antonio Gonzalez; Bjarni V. Halldorsson; Christina L. Hammond; Deborah J. Hart; Hafdis Helgadottir; Albert Hofman; Shiro Ikegawa; Thorvaldur Ingvarsson; Qing Jiang; Helgi Jonsson; Jaakko Kaprio; Hiroshi Kawaguchi; Kalle Kisand; Margreet Kloppenburg; Urho M. Kujala; L. Stefan Lohmander; John Loughlin; Frank P. Luyten; Akihiko Mabuchi; Andrew McCaskie; Masahiro Nakajima; Peter M. Nilsson; Nao Nishida; William E. R. Ollier; Kalliope Panoutsopoulou; Tom van de Putte; Stuart H. Ralston; Fernado Rivadeneira; Janna Saarela; Stefan Schulte-Merker; Dongquan Shi; P. Eline Slagboom; Akihiro Sudo; Agu Tamm; Ann Tamm; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Aspasia Tsezou; Gillian A. Wallis; J. Mark Wilkinson; Noriko Yoshimura; Eleftheria Zeggini; Guangju Zhai; Feng Zhang; Ingileif Jonsdottir; Andre G. Uitterlinden; David T. Felson; Joyce B. van Meurs; Kari Stefansson; John P. A. Ioannidis; Timothy D. Spector

doi:10.1136/ard.2010.132787

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

Evangelos Evangelou, Ana M. Valdes, Hanneke J. M. Kerkhof, Unnur Styrkarsdottir, YanYan Zhu, Ingrid Meulenbelt, Rik J. Lories, Fotini B. Karassa, Przemko Tylzanowski, Steffan D. Bos, Toru Akune, Nigel K. Arden, Andrew Carr, Kay Chapman, L. Adrienne Cupples, Jin Dai, Panos Deloukas, Michael Doherty, Sally Doherty, Gunnar EngstromAntonio Gonzalez, Bjarni V. Halldorsson, Christina L. Hammond, Deborah J. Hart, Hafdis Helgadottir, Albert Hofman, Shiro Ikegawa, Thorvaldur Ingvarsson, Qing Jiang, Helgi Jonsson, Jaakko Kaprio, Hiroshi Kawaguchi, Kalle Kisand, Margreet Kloppenburg, Urho M. Kujala, L. Stefan Lohmander, John Loughlin, Frank P. Luyten, Akihiko Mabuchi, Andrew McCaskie, Masahiro Nakajima, Peter M. Nilsson, Nao Nishida, William E. R. Ollier, Kalliope Panoutsopoulou, Tom van de Putte, Stuart H. Ralston, Fernado Rivadeneira, Janna Saarela, Stefan Schulte-Merker, Dongquan Shi, P. Eline Slagboom, Akihiro Sudo, Agu Tamm, Ann Tamm, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Aspasia Tsezou, Gillian A. Wallis, J. Mark Wilkinson, Noriko Yoshimura, Eleftheria Zeggini, Guangju Zhai, Feng Zhang, Ingileif Jonsdottir, Andre G. Uitterlinden, David T. Felson, Joyce B. van Meurs, Kari Stefansson, John P. A. Ioannidis, Timothy D. Spector

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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.

Original language	English
Pages (from-to)	349 - 355
Number of pages	7
Journal	Annals of the Rheumatic Diseases
Volume	70
Issue number	2
DOIs	https://doi.org/10.1136/ard.2010.132787
Publication status	Published - Feb 2011

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Evangelou, E., Valdes, A. M., Kerkhof, H. J. M., Styrkarsdottir, U., Zhu, Y., Meulenbelt, I., Lories, R. J., Karassa, F. B., Tylzanowski, P., Bos, S. D., Akune, T., Arden, N. K., Carr, A., Chapman, K., Cupples, L. A., Dai, J., Deloukas, P., Doherty, M., Doherty, S., ... Spector, T. D. (2011). Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22. Annals of the Rheumatic Diseases, 70(2), 349 - 355. https://doi.org/10.1136/ard.2010.132787

@article{22dd77eeb932427ca348d28f9a22401b,

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

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 = "Evangelos Evangelou and Valdes, {Ana M.} and Kerkhof, {Hanneke J. M.} and Unnur Styrkarsdottir and YanYan Zhu and Ingrid Meulenbelt and Lories, {Rik J.} and Karassa, {Fotini B.} and Przemko Tylzanowski and Bos, {Steffan D.} and Toru Akune and Arden, {Nigel K.} and Andrew Carr and Kay Chapman and Cupples, {L. Adrienne} and Jin Dai and Panos Deloukas and Michael Doherty and Sally Doherty and Gunnar Engstrom and Antonio Gonzalez and Halldorsson, {Bjarni V.} and Hammond, {Christina L.} and Hart, {Deborah J.} and Hafdis Helgadottir and Albert Hofman and Shiro Ikegawa and Thorvaldur Ingvarsson and Qing Jiang and Helgi Jonsson and Jaakko Kaprio and Hiroshi Kawaguchi and Kalle Kisand and Margreet Kloppenburg and Kujala, {Urho M.} and Lohmander, {L. Stefan} and John Loughlin and Luyten, {Frank P.} and Akihiko Mabuchi and Andrew McCaskie and Masahiro Nakajima and Nilsson, {Peter M.} and Nao Nishida and Ollier, {William E. R.} and Kalliope Panoutsopoulou and {van de Putte}, Tom and Ralston, {Stuart H.} and Fernado Rivadeneira and Janna Saarela and Stefan Schulte-Merker and Dongquan Shi and Slagboom, {P. Eline} and Akihiro Sudo and Agu Tamm and Ann Tamm and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Aspasia Tsezou and Wallis, {Gillian A.} and Wilkinson, {J. Mark} and Noriko Yoshimura and Eleftheria Zeggini and Guangju Zhai and Feng Zhang and Ingileif Jonsdottir and Uitterlinden, {Andre G.} and Felson, {David T.} and {van Meurs}, {Joyce B.} and Kari Stefansson and Ioannidis, {John P. A.} and Spector, {Timothy D.}",

year = "2011",

month = feb,

doi = "10.1136/ard.2010.132787",

language = "English",

volume = "70",

pages = "349 -- 355",

journal = "Annals of the Rheumatic Diseases",

issn = "1468-2060",

publisher = "BMJ Publishing Group",

number = "2",

}

Evangelou, E, Valdes, AM, Kerkhof, HJM, Styrkarsdottir, U, Zhu, Y, Meulenbelt, I, Lories, RJ, Karassa, FB, Tylzanowski, P, Bos, SD, Akune, T, Arden, NK, Carr, A, Chapman, K, Cupples, LA, Dai, J, Deloukas, P, Doherty, M, Doherty, S, Engstrom, G, Gonzalez, A, Halldorsson, BV, Hammond, CL, Hart, DJ, Helgadottir, H, Hofman, A, Ikegawa, S, Ingvarsson, T, Jiang, Q, Jonsson, H, Kaprio, J, Kawaguchi, H, Kisand, K, Kloppenburg, M, Kujala, UM, Lohmander, LS, Loughlin, J, Luyten, FP, Mabuchi, A, McCaskie, A, Nakajima, M, Nilsson, PM, Nishida, N, Ollier, WER, Panoutsopoulou, K, van de Putte, T, Ralston, SH, Rivadeneira, F, Saarela, J, Schulte-Merker, S, Shi, D, Slagboom, PE, Sudo, A, Tamm, A, Tamm, A, Thorleifsson, G, Thorsteinsdottir, U, Tsezou, A, Wallis, GA, Wilkinson, JM, Yoshimura, N, Zeggini, E, Zhai, G , Zhang, F, Jonsdottir, I, Uitterlinden, AG, Felson, DT, van Meurs, JB, Stefansson, K, Ioannidis, JPA & Spector, TD 2011, 'Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22', Annals of the Rheumatic Diseases, vol. 70, no. 2, pp. 349 - 355. https://doi.org/10.1136/ard.2010.132787

TY - JOUR

T1 - Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

AU - Evangelou, Evangelos

AU - Valdes, Ana M.

AU - Kerkhof, Hanneke J. M.

AU - Styrkarsdottir, Unnur

AU - Zhu, YanYan

AU - Meulenbelt, Ingrid

AU - Lories, Rik J.

AU - Karassa, Fotini B.

AU - Tylzanowski, Przemko

AU - Bos, Steffan D.

AU - Akune, Toru

AU - Arden, Nigel K.

AU - Carr, Andrew

AU - Chapman, Kay

AU - Cupples, L. Adrienne

AU - Dai, Jin

AU - Deloukas, Panos

AU - Doherty, Michael

AU - Doherty, Sally

AU - Engstrom, Gunnar

AU - Gonzalez, Antonio

AU - Halldorsson, Bjarni V.

AU - Hammond, Christina L.

AU - Hart, Deborah J.

AU - Helgadottir, Hafdis

AU - Hofman, Albert

AU - Ikegawa, Shiro

AU - Ingvarsson, Thorvaldur

AU - Jiang, Qing

AU - Jonsson, Helgi

AU - Kaprio, Jaakko

AU - Kawaguchi, Hiroshi

AU - Kisand, Kalle

AU - Kloppenburg, Margreet

AU - Kujala, Urho M.

AU - Lohmander, L. Stefan

AU - Loughlin, John

AU - Luyten, Frank P.

AU - Mabuchi, Akihiko

AU - McCaskie, Andrew

AU - Nakajima, Masahiro

AU - Nilsson, Peter M.

AU - Nishida, Nao

AU - Ollier, William E. R.

AU - Panoutsopoulou, Kalliope

AU - van de Putte, Tom

AU - Ralston, Stuart H.

AU - Rivadeneira, Fernado

AU - Saarela, Janna

AU - Schulte-Merker, Stefan

AU - Shi, Dongquan

AU - Slagboom, P. Eline

AU - Sudo, Akihiro

AU - Tamm, Agu

AU - Tamm, Ann

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - Tsezou, Aspasia

AU - Wallis, Gillian A.

AU - Wilkinson, J. Mark

AU - Yoshimura, Noriko

AU - Zeggini, Eleftheria

AU - Zhai, Guangju

AU - Zhang, Feng

AU - Jonsdottir, Ingileif

AU - Uitterlinden, Andre G.

AU - Felson, David T.

AU - van Meurs, Joyce B.

AU - Stefansson, Kari

AU - Ioannidis, John P. A.

AU - Spector, Timothy D.

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

U2 - 10.1136/ard.2010.132787

DO - 10.1136/ard.2010.132787

M3 - Article

SN - 1468-2060

VL - 70

SP - 349

EP - 355

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 2

ER -

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

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