Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci

V. Tragante; M.R. Barnes; S.K. Ganesh; M.B. Lanktree; W. Guo; N. Franceschini; E.N. Smith; T. Johnson; M.V. Holmes; S. Padmanabhan; K.J. Karczewski; B. Almoguera; J. Barnard; J. Baumert; Y.P.C. Chang; C.C. Elbers; M. Farrall; M.E. Fischer; T.R. Gaunt; J.M.I.H. Gho; C. Gieger; A. Goel; Y. Gong; A. Isaacs; M.E. Kleber; I.M. Leach; C.W. McDonough; M.F.L. Meijs; O. Melander; C.P. Nelson; I.M. Nolte; N. Pankratz; T.S. Price; J. Shaffer; S. Shah; M. Tomaszewski; P.J. van der Most; E.P.A. van Iperen; J.M. Vonk; K. Witkowska; C.O.L. Wong; L. Zhang; A.L. Beitelshees; G.S. Berenson; D.L. Bhatt; M. Brown; A. Burt; R.M. Cooper-DeHoff; J.M. Connell; K.J. Cruickshanks; S.P. Curtis; G. Davey-Smith; C. Delles; R.T. Gansevoort; X.Q. Guo; S. Haiqing; C.E. Hastie; M.H. Hofker; G.K. Hovingh; D.S. Kim; S.A. Kirkland; B.E. Klein; R. Klein; Y.R. Li; S. Maiwald; C. Newton-Cheh; E.T. O'Brien; N.C. Onland-Moret; W. Palmas; A. Parsa; B.W. Penninx; M. Pettinger; R.S. Vasan; J.E. Ranchalis; P.M. Ridker; L.M. Rose; P. Sever; D. Shimbo; L. Steele; R.P Stolk; B. Thorand; M.D. Trip; C.M. van Duijn; W.M. Verschuren; C. Wijmenga; S. Wyatt; J.H. Young; A.H. Zwinderman; C.R. Bezzina; E. Boerwinkle; J.P. Casas; M.J. Caulfield; A. Chakravarti; D.I. Chasman; K.W. Davidson; P.A. Doevendans; A.F. Dominiczak; G.A. FitzGerald; J.G. Gums; P.B. Munroe; B.J. Keating

doi:10.1016/j.ajhg.2013.12.016

Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci

V. Tragante, M.R. Barnes, S.K. Ganesh, M.B. Lanktree, W. Guo, N. Franceschini, E.N. Smith, T. Johnson, M.V. Holmes, S. Padmanabhan, K.J. Karczewski, B. Almoguera, J. Barnard, J. Baumert, Y.P.C. Chang, C.C. Elbers, M. Farrall, M.E. Fischer, T.R. Gaunt, J.M.I.H. GhoC. Gieger, A. Goel, Y. Gong, A. Isaacs, M.E. Kleber, I.M. Leach, C.W. McDonough, M.F.L. Meijs, O. Melander, C.P. Nelson, I.M. Nolte, N. Pankratz, T.S. Price, J. Shaffer, S. Shah, M. Tomaszewski, P.J. van der Most, E.P.A. van Iperen, J.M. Vonk, K. Witkowska, C.O.L. Wong, L. Zhang, A.L. Beitelshees, G.S. Berenson, D.L. Bhatt, M. Brown, A. Burt, R.M. Cooper-DeHoff, J.M. Connell, K.J. Cruickshanks, S.P. Curtis, G. Davey-Smith, C. Delles, R.T. Gansevoort, X.Q. Guo, S. Haiqing, C.E. Hastie, M.H. Hofker, G.K. Hovingh, D.S. Kim, S.A. Kirkland, B.E. Klein, R. Klein, Y.R. Li, S. Maiwald, C. Newton-Cheh, E.T. O'Brien, N.C. Onland-Moret, W. Palmas, A. Parsa, B.W. Penninx, M. Pettinger, R.S. Vasan, J.E. Ranchalis, P.M. Ridker, L.M. Rose, P. Sever, D. Shimbo, L. Steele, R.P Stolk, B. Thorand, M.D. Trip, C.M. van Duijn, W.M. Verschuren, C. Wijmenga, S. Wyatt, J.H. Young, A.H. Zwinderman, C.R. Bezzina, E. Boerwinkle, J.P. Casas, M.J. Caulfield, A. Chakravarti, D.I. Chasman, K.W. Davidson, P.A. Doevendans, A.F. Dominiczak, G.A. FitzGerald, J.G. Gums, P.B. Munroe, B.J. Keating

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Abstract

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10

Original language	English
Pages (from-to)	349-360
Journal	American Journal of Human Genetics
Volume	94
Issue number	3
DOIs	https://doi.org/10.1016/j.ajhg.2013.12.016
Publication status	Published - 2014

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10.1016/j.ajhg.2013.12.016

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Tragante, V., Barnes, M. R., Ganesh, S. K., Lanktree, M. B., Guo, W., Franceschini, N., Smith, E. N., Johnson, T., Holmes, M. V., Padmanabhan, S., Karczewski, K. J., Almoguera, B., Barnard, J., Baumert, J., Chang, Y. P. C., Elbers, C. C., Farrall, M., Fischer, M. E., Gaunt, T. R., ... Keating, B. J. (2014). Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci. American Journal of Human Genetics, 94(3), 349-360. https://doi.org/10.1016/j.ajhg.2013.12.016

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title = "Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci",

abstract = "Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10",

author = "V. Tragante and M.R. Barnes and S.K. Ganesh and M.B. Lanktree and W. Guo and N. Franceschini and E.N. Smith and T. Johnson and M.V. Holmes and S. Padmanabhan and K.J. Karczewski and B. Almoguera and J. Barnard and J. Baumert and Y.P.C. Chang and C.C. Elbers and M. Farrall and M.E. Fischer and T.R. Gaunt and J.M.I.H. Gho and C. Gieger and A. Goel and Y. Gong and A. Isaacs and M.E. Kleber and I.M. Leach and C.W. McDonough and M.F.L. Meijs and O. Melander and C.P. Nelson and I.M. Nolte and N. Pankratz and T.S. Price and J. Shaffer and S. Shah and M. Tomaszewski and {van der Most}, P.J. and {van Iperen}, E.P.A. and J.M. Vonk and K. Witkowska and C.O.L. Wong and L. Zhang and A.L. Beitelshees and G.S. Berenson and D.L. Bhatt and M. Brown and A. Burt and R.M. Cooper-DeHoff and J.M. Connell and K.J. Cruickshanks and S.P. Curtis and G. Davey-Smith and C. Delles and R.T. Gansevoort and X.Q. Guo and S. Haiqing and C.E. Hastie and M.H. Hofker and G.K. Hovingh and D.S. Kim and S.A. Kirkland and B.E. Klein and R. Klein and Y.R. Li and S. Maiwald and C. Newton-Cheh and E.T. O'Brien and N.C. Onland-Moret and W. Palmas and A. Parsa and B.W. Penninx and M. Pettinger and R.S. Vasan and J.E. Ranchalis and P.M. Ridker and L.M. Rose and P. Sever and D. Shimbo and L. Steele and R.P Stolk and B. Thorand and M.D. Trip and {van Duijn}, C.M. and W.M. Verschuren and C. Wijmenga and S. Wyatt and J.H. Young and A.H. Zwinderman and C.R. Bezzina and E. Boerwinkle and J.P. Casas and M.J. Caulfield and A. Chakravarti and D.I. Chasman and K.W. Davidson and P.A. Doevendans and A.F. Dominiczak and G.A. FitzGerald and J.G. Gums and P.B. Munroe and B.J. Keating",

year = "2014",

doi = "10.1016/j.ajhg.2013.12.016",

language = "English",

volume = "94",

pages = "349--360",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "3",

}

Tragante, V, Barnes, MR, Ganesh, SK, Lanktree, MB, Guo, W, Franceschini, N, Smith, EN, Johnson, T, Holmes, MV, Padmanabhan, S, Karczewski, KJ, Almoguera, B, Barnard, J, Baumert, J, Chang, YPC, Elbers, CC, Farrall, M, Fischer, ME, Gaunt, TR, Gho, JMIH, Gieger, C, Goel, A, Gong, Y, Isaacs, A, Kleber, ME, Leach, IM, McDonough, CW, Meijs, MFL, Melander, O, Nelson, CP, Nolte, IM, Pankratz, N, Price, TS, Shaffer, J, Shah, S, Tomaszewski, M, van der Most, PJ, van Iperen, EPA, Vonk, JM, Witkowska, K, Wong, COL, Zhang, L, Beitelshees, AL, Berenson, GS, Bhatt, DL, Brown, M, Burt, A, Cooper-DeHoff, RM, Connell, JM, Cruickshanks, KJ, Curtis, SP, Davey-Smith, G, Delles, C, Gansevoort, RT, Guo, XQ, Haiqing, S, Hastie, CE, Hofker, MH, Hovingh, GK, Kim, DS, Kirkland, SA, Klein, BE, Klein, R, Li, YR, Maiwald, S, Newton-Cheh, C, O'Brien, ET, Onland-Moret, NC, Palmas, W, Parsa, A, Penninx, BW, Pettinger, M, Vasan, RS, Ranchalis, JE, Ridker, PM, Rose, LM, Sever, P, Shimbo, D, Steele, L, Stolk, RP, Thorand, B, Trip, MD, van Duijn, CM, Verschuren, WM, Wijmenga, C, Wyatt, S, Young, JH, Zwinderman, AH, Bezzina, CR, Boerwinkle, E, Casas, JP, Caulfield, MJ, Chakravarti, A, Chasman, DI, Davidson, KW, Doevendans, PA, Dominiczak, AF, FitzGerald, GA, Gums, JG, Munroe, PB & Keating, BJ 2014, 'Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci', American Journal of Human Genetics, vol. 94, no. 3, pp. 349-360. https://doi.org/10.1016/j.ajhg.2013.12.016

TY - JOUR

T1 - Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci

AU - Tragante, V.

AU - Barnes, M.R.

AU - Ganesh, S.K.

AU - Lanktree, M.B.

AU - Guo, W.

AU - Franceschini, N.

AU - Smith, E.N.

AU - Johnson, T.

AU - Holmes, M.V.

AU - Padmanabhan, S.

AU - Karczewski, K.J.

AU - Almoguera, B.

AU - Barnard, J.

AU - Baumert, J.

AU - Chang, Y.P.C.

AU - Elbers, C.C.

AU - Farrall, M.

AU - Fischer, M.E.

AU - Gaunt, T.R.

AU - Gho, J.M.I.H.

AU - Gieger, C.

AU - Goel, A.

AU - Gong, Y.

AU - Isaacs, A.

AU - Kleber, M.E.

AU - Leach, I.M.

AU - McDonough, C.W.

AU - Meijs, M.F.L.

AU - Melander, O.

AU - Nelson, C.P.

AU - Nolte, I.M.

AU - Pankratz, N.

AU - Price, T.S.

AU - Shaffer, J.

AU - Shah, S.

AU - Tomaszewski, M.

AU - van der Most, P.J.

AU - van Iperen, E.P.A.

AU - Vonk, J.M.

AU - Witkowska, K.

AU - Wong, C.O.L.

AU - Zhang, L.

AU - Beitelshees, A.L.

AU - Berenson, G.S.

AU - Bhatt, D.L.

AU - Brown, M.

AU - Burt, A.

AU - Cooper-DeHoff, R.M.

AU - Connell, J.M.

AU - Cruickshanks, K.J.

AU - Curtis, S.P.

AU - Davey-Smith, G.

AU - Delles, C.

AU - Gansevoort, R.T.

AU - Guo, X.Q.

AU - Haiqing, S.

AU - Hastie, C.E.

AU - Hofker, M.H.

AU - Hovingh, G.K.

AU - Kim, D.S.

AU - Kirkland, S.A.

AU - Klein, B.E.

AU - Klein, R.

AU - Li, Y.R.

AU - Maiwald, S.

AU - Newton-Cheh, C.

AU - O'Brien, E.T.

AU - Onland-Moret, N.C.

AU - Palmas, W.

AU - Parsa, A.

AU - Penninx, B.W.

AU - Pettinger, M.

AU - Vasan, R.S.

AU - Ranchalis, J.E.

AU - Ridker, P.M.

AU - Rose, L.M.

AU - Sever, P.

AU - Shimbo, D.

AU - Steele, L.

AU - Stolk, R.P

AU - Thorand, B.

AU - Trip, M.D.

AU - van Duijn, C.M.

AU - Verschuren, W.M.

AU - Wijmenga, C.

AU - Wyatt, S.

AU - Young, J.H.

AU - Zwinderman, A.H.

AU - Bezzina, C.R.

AU - Boerwinkle, E.

AU - Casas, J.P.

AU - Caulfield, M.J.

AU - Chakravarti, A.

AU - Chasman, D.I.

AU - Davidson, K.W.

AU - Doevendans, P.A.

AU - Dominiczak, A.F.

AU - FitzGerald, G.A.

AU - Gums, J.G.

AU - Munroe, P.B.

AU - Keating, B.J.

PY - 2014

Y1 - 2014

N2 - Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10

AB - Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10

U2 - 10.1016/j.ajhg.2013.12.016

DO - 10.1016/j.ajhg.2013.12.016

M3 - Article

SN - 0002-9297

VL - 94

SP - 349

EP - 360

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 3

ER -

Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci

Abstract

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