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Genome-wide association study meta-analysis of chronic widespread pain

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Genome-wide association study meta-analysis of chronic widespread pain : evidence for involvement of the 5p15.2 region. / Peters, M.J.; Broer, L.; Willemen, H.L.D.M.; Eiriksdottir, G.; Hocking, L.J.; Holliday, K.L.; Horan, M.A.; Meulenbelt, I.; Neogi, T.; Popham, M.; Schmidt, C.O.; Soni, A.; Valdes, A.M.; Amin, N.; Dennison, E.M.; Eijkelkamp, N.; Harris, T.B.; Hart, D.J.; Hofman, A.; Huygen, F.J.P.M.; Jameson, K.A.; Jones, G.T.; Launer, L.J.; Kerkhof, H.J.M.; De Kruijf, M.; McBeth, J.; Kloppenburg, M.; Ollier, W.E.; Oostra, B.; Payton, A.; Rivadeneira, F.; Smith, Blair H; Smith, A.V.; Stolk, L.; Teumer, A.; Thomson, W.; Uitterlinden, A.G.; Wang, K.; Van Wingerden, S.H.; Arden, N.K.; Cooper, C.; Felson, D.; Gudnason, V.; Macfarlane, G.J.; Pendleton, N.; Slagboom, P.E.; Spector, T.D.; Völzke, H.; Kavelaars, A.; Van Duijn, C.M.; Williams, F.M.K.; Van Meurs, J.B.J.

In: Annals of the Rheumatic Diseases, Vol. 72, No. 3, 03.2013, p. 427-436.

Research output: Contribution to journalArticle

Harvard

Peters, MJ, Broer, L, Willemen, HLDM, Eiriksdottir, G, Hocking, LJ, Holliday, KL, Horan, MA, Meulenbelt, I, Neogi, T, Popham, M, Schmidt, CO, Soni, A, Valdes, AM, Amin, N, Dennison, EM, Eijkelkamp, N, Harris, TB, Hart, DJ, Hofman, A, Huygen, FJPM, Jameson, KA, Jones, GT, Launer, LJ, Kerkhof, HJM, De Kruijf, M, McBeth, J, Kloppenburg, M, Ollier, WE, Oostra, B, Payton, A, Rivadeneira, F, Smith, BH, Smith, AV, Stolk, L, Teumer, A, Thomson, W, Uitterlinden, AG, Wang, K, Van Wingerden, SH, Arden, NK, Cooper, C, Felson, D, Gudnason, V, Macfarlane, GJ, Pendleton, N, Slagboom, PE, Spector, TD, Völzke, H, Kavelaars, A, Van Duijn, CM, Williams, FMK & Van Meurs, JBJ 2013, 'Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region' Annals of the Rheumatic Diseases, vol 72, no. 3, pp. 427-436., 10.1136/annrheumdis-2012-201742

APA

Peters, M. J., Broer, L., Willemen, H. L. D. M., Eiriksdottir, G., Hocking, L. J., Holliday, K. L., ... Van Meurs, J. B. J. (2013). Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region. Annals of the Rheumatic Diseases, 72(3), 427-436. 10.1136/annrheumdis-2012-201742

Vancouver

Peters MJ, Broer L, Willemen HLDM, Eiriksdottir G, Hocking LJ, Holliday KL et al. Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region. Annals of the Rheumatic Diseases. 2013 Mar;72(3):427-436. Available from: 10.1136/annrheumdis-2012-201742

Author

Peters, M.J.; Broer, L.; Willemen, H.L.D.M.; Eiriksdottir, G.; Hocking, L.J.; Holliday, K.L.; Horan, M.A.; Meulenbelt, I.; Neogi, T.; Popham, M.; Schmidt, C.O.; Soni, A.; Valdes, A.M.; Amin, N.; Dennison, E.M.; Eijkelkamp, N.; Harris, T.B.; Hart, D.J.; Hofman, A.; Huygen, F.J.P.M.; Jameson, K.A.; Jones, G.T.; Launer, L.J.; Kerkhof, H.J.M.; De Kruijf, M.; McBeth, J.; Kloppenburg, M.; Ollier, W.E.; Oostra, B.; Payton, A.; Rivadeneira, F.; Smith, Blair H; Smith, A.V.; Stolk, L.; Teumer, A.; Thomson, W.; Uitterlinden, A.G.; Wang, K.; Van Wingerden, S.H.; Arden, N.K.; Cooper, C.; Felson, D.; Gudnason, V.; Macfarlane, G.J.; Pendleton, N.; Slagboom, P.E.; Spector, T.D.; Völzke, H.; Kavelaars, A.; Van Duijn, C.M.; Williams, F.M.K.; Van Meurs, J.B.J. / Genome-wide association study meta-analysis of chronic widespread pain : evidence for involvement of the 5p15.2 region.

In: Annals of the Rheumatic Diseases, Vol. 72, No. 3, 03.2013, p. 427-436.

Research output: Contribution to journalArticle

Bibtex - Download

@article{098f6d5ef26c4c96ae0119a0232de5eb,
title = "Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region",
author = "M.J. Peters and L. Broer and H.L.D.M. Willemen and G. Eiriksdottir and L.J. Hocking and K.L. Holliday and M.A. Horan and I. Meulenbelt and T. Neogi and M. Popham and C.O. Schmidt and A. Soni and A.M. Valdes and N. Amin and E.M. Dennison and N. Eijkelkamp and T.B. Harris and D.J. Hart and A. Hofman and F.J.P.M. Huygen and K.A. Jameson and G.T. Jones and L.J. Launer and H.J.M. Kerkhof and {De Kruijf}, M. and J. McBeth and M. Kloppenburg and W.E. Ollier and B. Oostra and A. Payton and F. Rivadeneira and Smith, {Blair H} and A.V. Smith and L. Stolk and A. Teumer and W. Thomson and A.G. Uitterlinden and K. Wang and {Van Wingerden}, S.H. and N.K. Arden and C. Cooper and D. Felson and V. Gudnason and G.J. Macfarlane and N. Pendleton and P.E. Slagboom and T.D. Spector and H. Völzke and A. Kavelaars and {Van Duijn}, C.M. and F.M.K. Williams and {Van Meurs}, J.B.J.",
note = "Copyright 2013 Elsevier B.V., All rights reserved.",
year = "2013",
doi = "10.1136/annrheumdis-2012-201742",
volume = "72",
number = "3",
pages = "427--436",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Genome-wide association study meta-analysis of chronic widespread pain

T2 - evidence for involvement of the 5p15.2 region

A1 - Peters,M.J.

A1 - Broer,L.

A1 - Willemen,H.L.D.M.

A1 - Eiriksdottir,G.

A1 - Hocking,L.J.

A1 - Holliday,K.L.

A1 - Horan,M.A.

A1 - Meulenbelt,I.

A1 - Neogi,T.

A1 - Popham,M.

A1 - Schmidt,C.O.

A1 - Soni,A.

A1 - Valdes,A.M.

A1 - Amin,N.

A1 - Dennison,E.M.

A1 - Eijkelkamp,N.

A1 - Harris,T.B.

A1 - Hart,D.J.

A1 - Hofman,A.

A1 - Huygen,F.J.P.M.

A1 - Jameson,K.A.

A1 - Jones,G.T.

A1 - Launer,L.J.

A1 - Kerkhof,H.J.M.

A1 - De Kruijf,M.

A1 - McBeth,J.

A1 - Kloppenburg,M.

A1 - Ollier,W.E.

A1 - Oostra,B.

A1 - Payton,A.

A1 - Rivadeneira,F.

A1 - Smith,Blair H

A1 - Smith,A.V.

A1 - Stolk,L.

A1 - Teumer,A.

A1 - Thomson,W.

A1 - Uitterlinden,A.G.

A1 - Wang,K.

A1 - Van Wingerden,S.H.

A1 - Arden,N.K.

A1 - Cooper,C.

A1 - Felson,D.

A1 - Gudnason,V.

A1 - Macfarlane,G.J.

A1 - Pendleton,N.

A1 - Slagboom,P.E.

A1 - Spector,T.D.

A1 - Völzke,H.

A1 - Kavelaars,A.

A1 - Van Duijn,C.M.

A1 - Williams,F.M.K.

A1 - Van Meurs,J.B.J.

AU - Peters,M.J.

AU - Broer,L.

AU - Willemen,H.L.D.M.

AU - Eiriksdottir,G.

AU - Hocking,L.J.

AU - Holliday,K.L.

AU - Horan,M.A.

AU - Meulenbelt,I.

AU - Neogi,T.

AU - Popham,M.

AU - Schmidt,C.O.

AU - Soni,A.

AU - Valdes,A.M.

AU - Amin,N.

AU - Dennison,E.M.

AU - Eijkelkamp,N.

AU - Harris,T.B.

AU - Hart,D.J.

AU - Hofman,A.

AU - Huygen,F.J.P.M.

AU - Jameson,K.A.

AU - Jones,G.T.

AU - Launer,L.J.

AU - Kerkhof,H.J.M.

AU - De Kruijf,M.

AU - McBeth,J.

AU - Kloppenburg,M.

AU - Ollier,W.E.

AU - Oostra,B.

AU - Payton,A.

AU - Rivadeneira,F.

AU - Smith,Blair H

AU - Smith,A.V.

AU - Stolk,L.

AU - Teumer,A.

AU - Thomson,W.

AU - Uitterlinden,A.G.

AU - Wang,K.

AU - Van Wingerden,S.H.

AU - Arden,N.K.

AU - Cooper,C.

AU - Felson,D.

AU - Gudnason,V.

AU - Macfarlane,G.J.

AU - Pendleton,N.

AU - Slagboom,P.E.

AU - Spector,T.D.

AU - Völzke,H.

AU - Kavelaars,A.

AU - Van Duijn,C.M.

AU - Williams,F.M.K.

AU - Van Meurs,J.B.J.

PY - 2013/3

Y1 - 2013/3

N2 - BACKGROUND AND OBJECTIVES: Chronic widespread pain (CWP) is a common disorder affecting ~10% of the general population and has an estimated heritability of 48-52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP. METHODS: We conducted a GWAS meta-analysis in 1308 female CWP cases and 5791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1480 CWP cases and 7989 controls. Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain. RESULTS: The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of chaperonin-containing-TCP1-complex-5 gene (CCT5) and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (minor allele frequency=43%; OR=1.30, 95% CI 1.19 to 1.42, p=1.2×10(-8)). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95% CI 1.10 to 1.24, p=4.7×10(-7)) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95% CI 1.14 to 1.32, p=3.4×10(-8), I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (p>7.7×10(-4)). CONCLUSIONS: We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.

AB - BACKGROUND AND OBJECTIVES: Chronic widespread pain (CWP) is a common disorder affecting ~10% of the general population and has an estimated heritability of 48-52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP. METHODS: We conducted a GWAS meta-analysis in 1308 female CWP cases and 5791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1480 CWP cases and 7989 controls. Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain. RESULTS: The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of chaperonin-containing-TCP1-complex-5 gene (CCT5) and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (minor allele frequency=43%; OR=1.30, 95% CI 1.19 to 1.42, p=1.2×10(-8)). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95% CI 1.10 to 1.24, p=4.7×10(-7)) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95% CI 1.14 to 1.32, p=3.4×10(-8), I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (p>7.7×10(-4)). CONCLUSIONS: We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.

UR - http://www.scopus.com/inward/record.url?scp=84873744735&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2012-201742

DO - 10.1136/annrheumdis-2012-201742

M1 - Article

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 3

VL - 72

SP - 427

EP - 436

ER -

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