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

E. Evangelou; A.M. Valdes; H.J. Kerkhof; U. Styrkarsdottir; Y. Zhu; I. Meulenbelt; R.J. Lories; F.B. Karassa; P. Tylzanowski; S.D. Bos; T. Akune; N.K. Arden; A. Carr; K. Chapman; L.A. Cupples; J. Dai; P. Deloukas; M. Doherty; S. Doherty; G. Engstrom; A. Gonzalez; B.V. Halldorsson; C.J. Hammond; D.J. Hart; H. Helgadottir; A. Hofman; S. Ikegawa; T. Ingvarsson; Q. Jiang; H. Jonsson; J. Kaprio; H. Kawaguchi; K. Kisand; M. Kloppenburg; U.M. Kujala; L.S. Lohmander; J. Loughlin; F.P. Luyten; A. Mabuchi; A. McCaskie; M. Nakajima; P.M. Nilsson; N. Nishida; W.E. Ollier; K. Panoutsopoulou; T. van de Putte; S.H. Ralston; F. Rivadeneira; J. Saarela; S. Schulte-Merker; D. Shi; P.E. Slagboom; A. Sudo; A. Tamm; G. Thorleifsson; U. Thorsteinsdottir; A. Tsezou; G.A. Wallis; J.M. Wilkinson; N. Yoshimura; E. Zeggini; G. Zhai; F. Zhang; I. Jonsdottir; A.G. Uitterlinden; D.T. Felson; J.B. van Meurs; K. Stefansson; J.P. Ioannidis; T.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

E. Evangelou, A.M. Valdes, H.J. Kerkhof, U. Styrkarsdottir, Y. Zhu, I. Meulenbelt, R.J. Lories, F.B. Karassa, P. Tylzanowski, S.D. Bos, T. Akune, N.K. Arden, A. Carr, K. Chapman, L.A. Cupples, J. Dai, P. Deloukas, M. Doherty, S. Doherty, G. EngstromA. Gonzalez, B.V. Halldorsson, C.J. Hammond, D.J. Hart, H. Helgadottir, A. Hofman, S. Ikegawa, T. Ingvarsson, Q. Jiang, H. Jonsson, J. Kaprio, H. Kawaguchi, K. Kisand, M. Kloppenburg, U.M. Kujala, L.S. Lohmander, J. Loughlin, F.P. Luyten, A. Mabuchi, A. McCaskie, M. Nakajima, P.M. Nilsson, N. Nishida, W.E. Ollier, K. Panoutsopoulou, T. van de Putte, S.H. Ralston, F. Rivadeneira, J. Saarela, S. Schulte-Merker, D. Shi, P.E. Slagboom, A. Sudo, A. Tamm, G. Thorleifsson, U. Thorsteinsdottir, A. Tsezou, G.A. Wallis, J.M. Wilkinson, N. Yoshimura, E. Zeggini, G. Zhai, F. Zhang, I. Jonsdottir, A.G. Uitterlinden, D.T. Felson, J.B. van Meurs, K. Stefansson, J.P. Ioannidis, T.D. Spector

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

116 Citations (Scopus)

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), 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]

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

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10.1136/ard.2010.132787

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Evangelou, E., Valdes, A. M., Kerkhof, H. J., 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{d1ab872877b84809af57363bb72010bb,

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), 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]",

author = "E. Evangelou and A.M. Valdes and H.J. Kerkhof and U. Styrkarsdottir and Y. Zhu and I. Meulenbelt and R.J. Lories and F.B. Karassa and P. Tylzanowski and S.D. Bos and T. Akune and N.K. Arden and A. Carr and K. Chapman and L.A. Cupples and J. Dai and P. Deloukas and M. Doherty and S. Doherty and G. Engstrom and A. Gonzalez and B.V. Halldorsson and C.J. Hammond and D.J. Hart and H. Helgadottir and A. Hofman and S. Ikegawa and T. Ingvarsson and Q. Jiang and H. Jonsson and J. Kaprio and H. Kawaguchi and K. Kisand and M. Kloppenburg and U.M. Kujala and L.S. Lohmander and J. Loughlin and F.P. Luyten and A. Mabuchi and A. McCaskie and M. Nakajima and P.M. Nilsson and N. Nishida and W.E. Ollier and K. Panoutsopoulou and {van de Putte}, T. and S.H. Ralston and F. Rivadeneira and J. Saarela and S. Schulte-Merker and D. Shi and P.E. Slagboom and A. Sudo and A. Tamm and G. Thorleifsson and U. Thorsteinsdottir and A. Tsezou and G.A. Wallis and J.M. Wilkinson and N. Yoshimura and E. Zeggini and G. Zhai and F. Zhang and I. Jonsdottir and A.G. Uitterlinden and D.T. Felson and {van Meurs}, J.B. and K. Stefansson and J.P. Ioannidis and T.D. Spector",

note = "Reporting year: 2011",

year = "2011",

doi = "10.1136/ard.2010.132787",

language = "English",

volume = "70",

pages = "349--355",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "BMJ Publishing Group",

number = "2",

}

Evangelou, E, Valdes, AM, Kerkhof, HJ, 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, CJ, 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, WE, Panoutsopoulou, K, van de Putte, T, Ralston, SH, Rivadeneira, F, Saarela, J, Schulte-Merker, S, Shi, D, Slagboom, PE, Sudo, 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, JP & 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, E.

AU - Valdes, A.M.

AU - Kerkhof, H.J.

AU - Styrkarsdottir, U.

AU - Zhu, Y.

AU - Meulenbelt, I.

AU - Lories, R.J.

AU - Karassa, F.B.

AU - Tylzanowski, P.

AU - Bos, S.D.

AU - Akune, T.

AU - Arden, N.K.

AU - Carr, A.

AU - Chapman, K.

AU - Cupples, L.A.

AU - Dai, J.

AU - Deloukas, P.

AU - Doherty, M.

AU - Doherty, S.

AU - Engstrom, G.

AU - Gonzalez, A.

AU - Halldorsson, B.V.

AU - Hammond, C.J.

AU - Hart, D.J.

AU - Helgadottir, H.

AU - Hofman, A.

AU - Ikegawa, S.

AU - Ingvarsson, T.

AU - Jiang, Q.

AU - Jonsson, H.

AU - Kaprio, J.

AU - Kawaguchi, H.

AU - Kisand, K.

AU - Kloppenburg, M.

AU - Kujala, U.M.

AU - Lohmander, L.S.

AU - Loughlin, J.

AU - Luyten, F.P.

AU - Mabuchi, A.

AU - McCaskie, A.

AU - Nakajima, M.

AU - Nilsson, P.M.

AU - Nishida, N.

AU - Ollier, W.E.

AU - Panoutsopoulou, K.

AU - van de Putte, T.

AU - Ralston, S.H.

AU - Rivadeneira, F.

AU - Saarela, J.

AU - Schulte-Merker, S.

AU - Shi, D.

AU - Slagboom, P.E.

AU - Sudo, A.

AU - Tamm, A.

AU - Thorleifsson, G.

AU - Thorsteinsdottir, U.

AU - Tsezou, A.

AU - Wallis, G.A.

AU - Wilkinson, J.M.

AU - Yoshimura, N.

AU - Zeggini, E.

AU - Zhai, G.

AU - Zhang, F.

AU - Jonsdottir, I.

AU - Uitterlinden, A.G.

AU - Felson, D.T.

AU - van Meurs, J.B.

AU - Stefansson, K.

AU - Ioannidis, J.P.

AU - Spector, T.D.

N1 - Reporting year: 2011

PY - 2011

Y1 - 2011

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), 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]

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), 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]

U2 - 10.1136/ard.2010.132787

DO - 10.1136/ard.2010.132787

M3 - Article

SN - 0003-4967

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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