Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data

G. Eiriksdottir; T.B. Harris; L.J. Launer; V. Gudnason; A.R. Folsom; G. Andrews; C.M. Ballantyne; N.J. Samani; A.S. Hall; P.S. Braund; A.J. Balmforth; P.H. Whincup; R. Morris; D.A. Lawlor; G.D.O. Lowe; N. Timpson; S. Ebrahim; Y. Ben-Shlomo; G. Davey-Smith; N. Timpson; B.G. Nordestgaard; A. Tybjærg-Hansen; J. Zacho; M. Brown; M. Sandhu; S.L. Ricketts; S. Ashford; L. Lange; A. Reiner; M. Cushman; R. Tracy; C. Wu; J. Ge; Y. Zou; A. Sun; J.Y. Hung; B. McQuillan; P. Thompson; J. Beilby; N. Warrington; L.J. Palmer; C. Wanner; C. Drechsler; M.M. Hoffmann; F.G.R. Fowkes; G.D.O. Lowe; I. Tzoulaki; M. Kumari; M. Miller; M. Marmot; C. Onland-Moret; Y.T. Van Der Schouw; J.M. Boer; C. Wijmenga; S.L. Ricketts; S. Ashford; M. Sandhu; K.-T. Khaw; R.S. Vasan; R.B. Schnabel; J.F. Yamamoto; E.J. Benjamin; H. Schunkert; J. Erdmann; I.R. König; C. Hengstenberg; B. Chiodini; M.G. Franzosi; S. Pietri; F. Gori; M. Rudock; Y. Liu; K. Lohman; T.B. Harris; S.E. Humphries; A. Hamsten; P.E. Norman; G.J. Hankey; K. Jamrozik; L.J. Palmer; E.B. Rimm; J.K. Pai; B.M. Psaty; S.R. Heckbert; J.C. Bis; S. Yusuf; S. Anand; J.C. Engert; C. Xie; R. Collins; R. Clarke; D. Bennett; J. Kooner; J. Chambers; P. Elliott; W. März; M.E. Kleber; B.O. Böhm; B.R. Winkelmann; O. Melander; G. Berglund; W. Koenig; B. Thorand; J. Baumert; A. Peters; E.B. Rimm; J. Manson; J.K. Pai; S.E. Humphries; J.A. Cooper; P.J. Talmud; P. Ladenvall; L. Johansson; J.-H. Jansson; G. Hallmans; M.P. Reilly; L. Qu; M. Li; D.J. Rader; H. Watkins; R. Clarke; J. Hopewell; D. Saleheen; J. Danesh; P. Frossard; N. Sattar; M. Robertson; J. Shepherd; E. Schaefer; A. Hofman; J.C.M. Witteman; I. Kardys; A. Dehghan; U. De Faire; A. Bennet; B. Gigante; K. Leander; Y. Ben-Shlomo; G. Davey-Smith; N. Timpson; B. Peters; A.H. Maitland-Van Der Zee; A. De Boer; O. Klungel; A. Reiner; J. Manson; P. Greenland; J. Dai; S. Liu; M. Kumari; E. Brunner; M. Kivimaki; M. Marmot; N. Sattar; D. O'Reilly; I. Ford; C.J. Packard

doi:10.1136/bmj.d548

Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data

G. Eiriksdottir, T.B. Harris, L.J. Launer, V. Gudnason, A.R. Folsom, G. Andrews, C.M. Ballantyne, N.J. Samani, A.S. Hall, P.S. Braund, A.J. Balmforth, P.H. Whincup, R. Morris, D.A. Lawlor, G.D.O. Lowe, N. Timpson, S. Ebrahim, Y. Ben-Shlomo, G. Davey-Smith, N. TimpsonB.G. Nordestgaard, A. Tybjærg-Hansen, J. Zacho, M. Brown, M. Sandhu, S.L. Ricketts, S. Ashford, L. Lange, A. Reiner, M. Cushman, R. Tracy, C. Wu, J. Ge, Y. Zou, A. Sun, J.Y. Hung, B. McQuillan, P. Thompson, J. Beilby, N. Warrington, L.J. Palmer, C. Wanner, C. Drechsler, M.M. Hoffmann, F.G.R. Fowkes, G.D.O. Lowe, I. Tzoulaki, M. Kumari, M. Miller, M. Marmot, C. Onland-Moret, Y.T. Van Der Schouw, J.M. Boer, C. Wijmenga, S.L. Ricketts, S. Ashford, M. Sandhu, K.-T. Khaw, R.S. Vasan, R.B. Schnabel, J.F. Yamamoto, E.J. Benjamin, H. Schunkert, J. Erdmann, I.R. König, C. Hengstenberg, B. Chiodini, M.G. Franzosi, S. Pietri, F. Gori, M. Rudock, Y. Liu, K. Lohman, T.B. Harris, S.E. Humphries, A. Hamsten, P.E. Norman, G.J. Hankey, K. Jamrozik, L.J. Palmer, E.B. Rimm, J.K. Pai, B.M. Psaty, S.R. Heckbert, J.C. Bis, S. Yusuf, S. Anand, J.C. Engert, C. Xie, R. Collins, R. Clarke, D. Bennett, J. Kooner, J. Chambers, P. Elliott, W. März, M.E. Kleber, B.O. Böhm, B.R. Winkelmann, O. Melander, G. Berglund, W. Koenig, B. Thorand, J. Baumert, A. Peters, E.B. Rimm, J. Manson, J.K. Pai, S.E. Humphries, J.A. Cooper, P.J. Talmud, P. Ladenvall, L. Johansson, J.-H. Jansson, G. Hallmans, M.P. Reilly, L. Qu, M. Li, D.J. Rader, H. Watkins, R. Clarke, J. Hopewell, D. Saleheen, J. Danesh, P. Frossard, N. Sattar, M. Robertson, J. Shepherd, E. Schaefer, A. Hofman, J.C.M. Witteman, I. Kardys, A. Dehghan, U. De Faire, A. Bennet, B. Gigante, K. Leander, Y. Ben-Shlomo, G. Davey-Smith, N. Timpson, B. Peters, A.H. Maitland-Van Der Zee, A. De Boer, O. Klungel, A. Reiner, J. Manson, P. Greenland, J. Dai, S. Liu, M. Kumari, E. Brunner, M. Kivimaki, M. Marmot, N. Sattar, D. O'Reilly, I. Ford, C.J. Packard

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Objective: To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design: Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries. Participants: 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors. Main outcome measures: Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals. Results: CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P

Original language	English
Article number	d548
Pages (from-to)	425
Number of pages	1
Journal	BMJ Open
Volume	342
Issue number	7794
DOIs	https://doi.org/10.1136/bmj.d548
Publication status	Published - 19 Feb 2011

Keywords

C reactive protein
adult
article
causal attribution
coronary risk
disease association
female
genetic risk
genetic variability
human
incidence
ischemic heart disease
major clinical study
male
Mendelian randomization analysis
prevalence
priority journal
risk factor
single nucleotide polymorphism

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10.1136/bmj.d548

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Eiriksdottir, G., Harris, T. B., Launer, L. J., Gudnason, V., Folsom, A. R., Andrews, G., Ballantyne, C. M., Samani, N. J., Hall, A. S., Braund, P. S., Balmforth, A. J., Whincup, P. H., Morris, R., Lawlor, D. A., Lowe, G. D. O., Timpson, N., Ebrahim, S., Ben-Shlomo, Y., Davey-Smith, G., ... Packard, C. J. (2011). Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data. BMJ Open, 342(7794), 425. Article d548. https://doi.org/10.1136/bmj.d548

@article{093f7383f3f842c4a168355ad24a7633,

title = "Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data",

abstract = "Objective: To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design: Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries. Participants: 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors. Main outcome measures: Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals. Results: CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P",

keywords = "C reactive protein, adult, article, causal attribution, coronary risk, disease association, female, genetic risk, genetic variability, human, incidence, ischemic heart disease, major clinical study, male, Mendelian randomization analysis, prevalence, priority journal, risk factor, single nucleotide polymorphism",

author = "G. Eiriksdottir and T.B. Harris and L.J. Launer and V. Gudnason and A.R. Folsom and G. Andrews and C.M. Ballantyne and N.J. Samani and A.S. Hall and P.S. Braund and A.J. Balmforth and P.H. Whincup and R. Morris and D.A. Lawlor and G.D.O. Lowe and N. Timpson and S. Ebrahim and Y. Ben-Shlomo and G. Davey-Smith and N. Timpson and B.G. Nordestgaard and A. Tybj{\ae}rg-Hansen and J. Zacho and M. Brown and M. Sandhu and S.L. Ricketts and S. Ashford and L. Lange and A. Reiner and M. Cushman and R. Tracy and C. Wu and J. Ge and Y. Zou and A. Sun and J.Y. Hung and B. McQuillan and P. Thompson and J. Beilby and N. Warrington and L.J. Palmer and C. Wanner and C. Drechsler and M.M. Hoffmann and F.G.R. Fowkes and G.D.O. Lowe and I. Tzoulaki and M. Kumari and M. Miller and M. Marmot and C. Onland-Moret and {Van Der Schouw}, Y.T. and J.M. Boer and C. Wijmenga and S.L. Ricketts and S. Ashford and M. Sandhu and K.-T. Khaw and R.S. Vasan and R.B. Schnabel and J.F. Yamamoto and E.J. Benjamin and H. Schunkert and J. Erdmann and I.R. K{\"o}nig and C. Hengstenberg and B. Chiodini and M.G. Franzosi and S. Pietri and F. Gori and M. Rudock and Y. Liu and K. Lohman and T.B. Harris and S.E. Humphries and A. Hamsten and P.E. Norman and G.J. Hankey and K. Jamrozik and L.J. Palmer and E.B. Rimm and J.K. Pai and B.M. Psaty and S.R. Heckbert and J.C. Bis and S. Yusuf and S. Anand and J.C. Engert and C. Xie and R. Collins and R. Clarke and D. Bennett and J. Kooner and J. Chambers and P. Elliott and W. M{\"a}rz and M.E. Kleber and B.O. B{\"o}hm and B.R. Winkelmann and O. Melander and G. Berglund and W. Koenig and B. Thorand and J. Baumert and A. Peters and E.B. Rimm and J. Manson and J.K. Pai and S.E. Humphries and J.A. Cooper and P.J. Talmud and P. Ladenvall and L. Johansson and J.-H. Jansson and G. Hallmans and M.P. Reilly and L. Qu and M. Li and D.J. Rader and H. Watkins and R. Clarke and J. Hopewell and D. Saleheen and J. Danesh and P. Frossard and N. Sattar and M. Robertson and J. Shepherd and E. Schaefer and A. Hofman and J.C.M. Witteman and I. Kardys and A. Dehghan and {De Faire}, U. and A. Bennet and B. Gigante and K. Leander and Y. Ben-Shlomo and G. Davey-Smith and N. Timpson and B. Peters and {Maitland-Van Der Zee}, A.H. and {De Boer}, A. and O. Klungel and A. Reiner and J. Manson and P. Greenland and J. Dai and S. Liu and M. Kumari and E. Brunner and M. Kivimaki and M. Marmot and N. Sattar and D. O'Reilly and I. Ford and C.J. Packard",

year = "2011",

month = feb,

day = "19",

doi = "10.1136/bmj.d548",

language = "English",

volume = "342",

pages = "425",

journal = "BMJ Open",

issn = "2044-6055",

publisher = "BMJ Publishing Group Ltd",

number = "7794",

}

Eiriksdottir, G, Harris, TB, Launer, LJ, Gudnason, V, Folsom, AR, Andrews, G, Ballantyne, CM, Samani, NJ, Hall, AS, Braund, PS, Balmforth, AJ, Whincup, PH, Morris, R, Lawlor, DA, Lowe, GDO, Timpson, N, Ebrahim, S, Ben-Shlomo, Y, Davey-Smith, G, Timpson, N, Nordestgaard, BG, Tybjærg-Hansen, A, Zacho, J, Brown, M, Sandhu, M, Ricketts, SL, Ashford, S, Lange, L, Reiner, A, Cushman, M, Tracy, R, Wu, C, Ge, J, Zou, Y, Sun, A, Hung, JY, McQuillan, B, Thompson, P, Beilby, J, Warrington, N, Palmer, LJ, Wanner, C, Drechsler, C, Hoffmann, MM, Fowkes, FGR, Lowe, GDO, Tzoulaki, I, Kumari, M, Miller, M, Marmot, M, Onland-Moret, C, Van Der Schouw, YT, Boer, JM, Wijmenga, C, Ricketts, SL, Ashford, S, Sandhu, M, Khaw, K-T, Vasan, RS, Schnabel, RB, Yamamoto, JF, Benjamin, EJ, Schunkert, H, Erdmann, J, König, IR, Hengstenberg, C, Chiodini, B, Franzosi, MG, Pietri, S, Gori, F, Rudock, M, Liu, Y, Lohman, K, Harris, TB, Humphries, SE, Hamsten, A, Norman, PE, Hankey, GJ, Jamrozik, K, Palmer, LJ, Rimm, EB, Pai, JK, Psaty, BM, Heckbert, SR, Bis, JC, Yusuf, S, Anand, S, Engert, JC, Xie, C, Collins, R, Clarke, R, Bennett, D, Kooner, J, Chambers, J, Elliott, P, März, W, Kleber, ME, Böhm, BO, Winkelmann, BR, Melander, O, Berglund, G, Koenig, W, Thorand, B, Baumert, J, Peters, A, Rimm, EB, Manson, J, Pai, JK, Humphries, SE, Cooper, JA, Talmud, PJ, Ladenvall, P, Johansson, L, Jansson, J-H, Hallmans, G, Reilly, MP, Qu, L, Li, M, Rader, DJ, Watkins, H, Clarke, R, Hopewell, J, Saleheen, D, Danesh, J, Frossard, P, Sattar, N, Robertson, M, Shepherd, J, Schaefer, E, Hofman, A, Witteman, JCM, Kardys, I, Dehghan, A, De Faire, U, Bennet, A, Gigante, B, Leander, K, Ben-Shlomo, Y, Davey-Smith, G, Timpson, N, Peters, B, Maitland-Van Der Zee, AH, De Boer, A, Klungel, O, Reiner, A, Manson, J, Greenland, P, Dai, J, Liu, S, Kumari, M, Brunner, E, Kivimaki, M, Marmot, M, Sattar, N, O'Reilly, D, Ford, I & Packard, CJ 2011, 'Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data', BMJ Open, vol. 342, no. 7794, d548, pp. 425. https://doi.org/10.1136/bmj.d548

TY - JOUR

T1 - Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data

AU - Eiriksdottir, G.

AU - Harris, T.B.

AU - Launer, L.J.

AU - Gudnason, V.

AU - Folsom, A.R.

AU - Andrews, G.

AU - Ballantyne, C.M.

AU - Samani, N.J.

AU - Hall, A.S.

AU - Braund, P.S.

AU - Balmforth, A.J.

AU - Whincup, P.H.

AU - Morris, R.

AU - Lawlor, D.A.

AU - Lowe, G.D.O.

AU - Timpson, N.

AU - Ebrahim, S.

AU - Ben-Shlomo, Y.

AU - Davey-Smith, G.

AU - Timpson, N.

AU - Nordestgaard, B.G.

AU - Tybjærg-Hansen, A.

AU - Zacho, J.

AU - Brown, M.

AU - Sandhu, M.

AU - Ricketts, S.L.

AU - Ashford, S.

AU - Lange, L.

AU - Reiner, A.

AU - Cushman, M.

AU - Tracy, R.

AU - Wu, C.

AU - Ge, J.

AU - Zou, Y.

AU - Sun, A.

AU - Hung, J.Y.

AU - McQuillan, B.

AU - Thompson, P.

AU - Beilby, J.

AU - Warrington, N.

AU - Palmer, L.J.

AU - Wanner, C.

AU - Drechsler, C.

AU - Hoffmann, M.M.

AU - Fowkes, F.G.R.

AU - Lowe, G.D.O.

AU - Tzoulaki, I.

AU - Kumari, M.

AU - Miller, M.

AU - Marmot, M.

AU - Onland-Moret, C.

AU - Van Der Schouw, Y.T.

AU - Boer, J.M.

AU - Wijmenga, C.

AU - Ricketts, S.L.

AU - Ashford, S.

AU - Sandhu, M.

AU - Khaw, K.-T.

AU - Vasan, R.S.

AU - Schnabel, R.B.

AU - Yamamoto, J.F.

AU - Benjamin, E.J.

AU - Schunkert, H.

AU - Erdmann, J.

AU - König, I.R.

AU - Hengstenberg, C.

AU - Chiodini, B.

AU - Franzosi, M.G.

AU - Pietri, S.

AU - Gori, F.

AU - Rudock, M.

AU - Liu, Y.

AU - Lohman, K.

AU - Harris, T.B.

AU - Humphries, S.E.

AU - Hamsten, A.

AU - Norman, P.E.

AU - Hankey, G.J.

AU - Jamrozik, K.

AU - Palmer, L.J.

AU - Rimm, E.B.

AU - Pai, J.K.

AU - Psaty, B.M.

AU - Heckbert, S.R.

AU - Bis, J.C.

AU - Yusuf, S.

AU - Anand, S.

AU - Engert, J.C.

AU - Xie, C.

AU - Collins, R.

AU - Clarke, R.

AU - Bennett, D.

AU - Kooner, J.

AU - Chambers, J.

AU - Elliott, P.

AU - März, W.

AU - Kleber, M.E.

AU - Böhm, B.O.

AU - Winkelmann, B.R.

AU - Melander, O.

AU - Berglund, G.

AU - Koenig, W.

AU - Thorand, B.

AU - Baumert, J.

AU - Peters, A.

AU - Rimm, E.B.

AU - Manson, J.

AU - Pai, J.K.

AU - Humphries, S.E.

AU - Cooper, J.A.

AU - Talmud, P.J.

AU - Ladenvall, P.

AU - Johansson, L.

AU - Jansson, J.-H.

AU - Hallmans, G.

AU - Reilly, M.P.

AU - Qu, L.

AU - Li, M.

AU - Rader, D.J.

AU - Watkins, H.

AU - Clarke, R.

AU - Hopewell, J.

AU - Saleheen, D.

AU - Danesh, J.

AU - Frossard, P.

AU - Sattar, N.

AU - Robertson, M.

AU - Shepherd, J.

AU - Schaefer, E.

AU - Hofman, A.

AU - Witteman, J.C.M.

AU - Kardys, I.

AU - Dehghan, A.

AU - De Faire, U.

AU - Bennet, A.

AU - Gigante, B.

AU - Leander, K.

AU - Ben-Shlomo, Y.

AU - Davey-Smith, G.

AU - Timpson, N.

AU - Peters, B.

AU - Maitland-Van Der Zee, A.H.

AU - De Boer, A.

AU - Klungel, O.

AU - Reiner, A.

AU - Manson, J.

AU - Greenland, P.

AU - Dai, J.

AU - Liu, S.

AU - Kumari, M.

AU - Brunner, E.

AU - Kivimaki, M.

AU - Marmot, M.

AU - Sattar, N.

AU - O'Reilly, D.

AU - Ford, I.

AU - Packard, C.J.

PY - 2011/2/19

Y1 - 2011/2/19

N2 - Objective: To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design: Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries. Participants: 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors. Main outcome measures: Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals. Results: CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P

AB - Objective: To use genetic variants as unconfounded proxies of C reactive protein concentration to study its causal role in coronary heart disease. Design: Mendelian randomisation meta-analysis of individual participant data from 47 epidemiological studies in 15 countries. Participants: 194 418 participants, including 46 557 patients with prevalent or incident coronary heart disease. Information was available on four CRP gene tagging single nucleotide polymorphisms (rs3093077, rs1205, rs1130864, rs1800947), concentration of C reactive protein, and levels of other risk factors. Main outcome measures: Risk ratios for coronary heart disease associated with genetically raised C reactive protein versus risk ratios with equivalent differences in C reactive protein concentration itself, adjusted for conventional risk factors and variability in risk factor levels within individuals. Results: CRP variants were each associated with up to 30% per allele difference in concentration of C reactive protein (P

KW - C reactive protein

KW - adult

KW - article

KW - causal attribution

KW - coronary risk

KW - disease association

KW - female

KW - genetic risk

KW - genetic variability

KW - human

KW - incidence

KW - ischemic heart disease

KW - major clinical study

KW - male

KW - Mendelian randomization analysis

KW - prevalence

KW - priority journal

KW - risk factor

KW - single nucleotide polymorphism

U2 - 10.1136/bmj.d548

DO - 10.1136/bmj.d548

M3 - Article

SN - 2044-6055

VL - 342

SP - 425

JO - BMJ Open

JF - BMJ Open

IS - 7794

M1 - d548

ER -

Association between C reactive protein and coronary heart disease: Mendelian randomisation analysis based on individual participant data

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Keywords

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