Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis

Eveline Nüesch; Caroline Dale; Tom M. Palmer; Jon White; Brendan J. Keating; Erik Pa van Iperen; Anuj Goel; Sandosh Padmanabhan; Folkert W. Asselbergs; W. M. Verschuren; C. Wijmenga; Y. T. van der Schouw; N. C. Onland-Moret; Leslie A. Lange; G. K. Hovingh; Suthesh Sivapalaratnam; Richard W. Morris; Peter H. Whincup; Goya S. Wannamethe; Tom R. Gaunt; Shah Ebrahim; Laura Steel; Nikhil Nair; Alexander P. Reiner; Charles Kooperberg; James F. Wilson; Jennifer L. Bolton; Stela McLachlan; Jacqueline F. Price; Mark Wj Strachan; Christine M. Robertson; Marcus E. Kleber; Graciela Delgado; Winfried März; Olle Melander; Anna F. Dominiczak; Martin Farrall; Hugh Watkins; Maarten Leusink; Anke H. Maitland-van der Zee; Mark Ch de Groot; Frank Dudbridge; Aroon Hingorani; Yoav Ben-Shlomo; Debbie A. Lawlor; A. Amuzu; M. Caufield; A. Cavadino; J. Cooper; T. L. Davies; F. Drenos; J. Engmann; C. Finan; C. Giambartolomei; R. Hardy; S. E. Humphries; E. Hypponen; M. Kivimaki; D. Kuh; M. Kumari; K. Ong; V. Plagnol; C. Power; M. Richards; S. Shah; T. Shah; R. Sofat; P. J. Talmud; N. Wareham; H. Warren; J. C. Whittaker; A. Wong; D. Zabaneh; George Davey Smith; Jonathan C. Wells; David A. Leon; Michael V. Holmes; Juan P. Casas

doi:https://doi.org/10.1093/ije/dyv074

Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis

Eveline Nüesch, Caroline Dale, Tom M. Palmer, Jon White, Brendan J. Keating, Erik Pa van Iperen, Anuj Goel, Sandosh Padmanabhan, Folkert W. Asselbergs, W. M. Verschuren, C. Wijmenga, Y. T. van der Schouw, N. C. Onland-Moret, Leslie A. Lange, G. K. Hovingh, Suthesh Sivapalaratnam, Richard W. Morris, Peter H. Whincup, Goya S. Wannamethe, Tom R. GauntShah Ebrahim, Laura Steel, Nikhil Nair, Alexander P. Reiner, Charles Kooperberg, James F. Wilson, Jennifer L. Bolton, Stela McLachlan, Jacqueline F. Price, Mark Wj Strachan, Christine M. Robertson, Marcus E. Kleber, Graciela Delgado, Winfried März, Olle Melander, Anna F. Dominiczak, Martin Farrall, Hugh Watkins, Maarten Leusink, Anke H. Maitland-van der Zee, Mark Ch de Groot, Frank Dudbridge, Aroon Hingorani, Yoav Ben-Shlomo, Debbie A. Lawlor, A. Amuzu, M. Caufield, A. Cavadino, J. Cooper, T. L. Davies, F. Drenos, J. Engmann, C. Finan, C. Giambartolomei, R. Hardy, S. E. Humphries, E. Hypponen, M. Kivimaki, D. Kuh, M. Kumari, K. Ong, V. Plagnol, C. Power, M. Richards, S. Shah, T. Shah, R. Sofat, P. J. Talmud, N. Wareham, H. Warren, J. C. Whittaker, A. Wong, D. Zabaneh, George Davey Smith, Jonathan C. Wells, David A. Leon, Michael V. Holmes, Juan P. Casas

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Abstract

We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index ( P < 0.001), triglycerides ( P < 0.001), non high-density (non-HDL) cholesterol ( P < 0.001), C-reactive protein ( P = 0.042), and systolic blood pressure ( P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity ( P < 0.001 for both). Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure

Original language	English
Pages (from-to)	1927-1937
Journal	International journal of epidemiology
Volume	45
Issue number	6
Early online date	2016
DOIs	https://doi.org/10.1093/ije/dyv074
Publication status	Published - 2016

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Nüesch, E., Dale, C., Palmer, T. M., White, J., Keating, B. J., van Iperen, E. P., Goel, A., Padmanabhan, S., Asselbergs, F. W., Verschuren, W. M., Wijmenga, C., van der Schouw, Y. T., Onland-Moret, N. C., Lange, L. A., Hovingh, G. K., Sivapalaratnam, S., Morris, R. W., Whincup, P. H., Wannamethe, G. S., ... Casas, J. P. (2016). Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis. International journal of epidemiology, 45(6), 1927-1937. https://doi.org/10.1093/ije/dyv074

@article{d88bd7259e6a4d69bbf6a62e671f7d1c,

title = "Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis",

abstract = "We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index ( P < 0.001), triglycerides ( P < 0.001), non high-density (non-HDL) cholesterol ( P < 0.001), C-reactive protein ( P = 0.042), and systolic blood pressure ( P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity ( P < 0.001 for both). Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure",

author = "Eveline N{\"u}esch and Caroline Dale and Palmer, {Tom M.} and Jon White and Keating, {Brendan J.} and {van Iperen}, {Erik Pa} and Anuj Goel and Sandosh Padmanabhan and Asselbergs, {Folkert W.} and Verschuren, {W. M.} and C. Wijmenga and {van der Schouw}, {Y. T.} and Onland-Moret, {N. C.} and Lange, {Leslie A.} and Hovingh, {G. K.} and Suthesh Sivapalaratnam and Morris, {Richard W.} and Whincup, {Peter H.} and Wannamethe, {Goya S.} and Gaunt, {Tom R.} and Shah Ebrahim and Laura Steel and Nikhil Nair and Reiner, {Alexander P.} and Charles Kooperberg and Wilson, {James F.} and Bolton, {Jennifer L.} and Stela McLachlan and Price, {Jacqueline F.} and Strachan, {Mark Wj} and Robertson, {Christine M.} and Kleber, {Marcus E.} and Graciela Delgado and Winfried M{\"a}rz and Olle Melander and Dominiczak, {Anna F.} and Martin Farrall and Hugh Watkins and Maarten Leusink and {Maitland-van der Zee}, {Anke H.} and {de Groot}, {Mark Ch} and Frank Dudbridge and Aroon Hingorani and Yoav Ben-Shlomo and Lawlor, {Debbie A.} and A. Amuzu and M. Caufield and A. Cavadino and J. Cooper and Davies, {T. L.} and F. Drenos and J. Engmann and C. Finan and C. Giambartolomei and R. Hardy and Humphries, {S. E.} and E. Hypponen and M. Kivimaki and D. Kuh and M. Kumari and K. Ong and V. Plagnol and C. Power and M. Richards and S. Shah and T. Shah and R. Sofat and Talmud, {P. J.} and N. Wareham and H. Warren and Whittaker, {J. C.} and A. Wong and D. Zabaneh and {Davey Smith}, George and Wells, {Jonathan C.} and Leon, {David A.} and Holmes, {Michael V.} and Casas, {Juan P.}",

year = "2016",

doi = "https://doi.org/10.1093/ije/dyv074",

language = "English",

volume = "45",

pages = "1927--1937",

journal = "International journal of epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "6",

}

Nüesch, E, Dale, C, Palmer, TM, White, J, Keating, BJ, van Iperen, EP, Goel, A, Padmanabhan, S, Asselbergs, FW, Verschuren, WM, Wijmenga, C, van der Schouw, YT, Onland-Moret, NC, Lange, LA, Hovingh, GK, Sivapalaratnam, S, Morris, RW, Whincup, PH, Wannamethe, GS, Gaunt, TR, Ebrahim, S, Steel, L, Nair, N, Reiner, AP, Kooperberg, C, Wilson, JF, Bolton, JL, McLachlan, S, Price, JF, Strachan, MW, Robertson, CM, Kleber, ME, Delgado, G, März, W, Melander, O, Dominiczak, AF, Farrall, M, Watkins, H, Leusink, M, Maitland-van der Zee, AH, de Groot, MC, Dudbridge, F, Hingorani, A, Ben-Shlomo, Y, Lawlor, DA, Amuzu, A, Caufield, M, Cavadino, A, Cooper, J, Davies, TL, Drenos, F, Engmann, J, Finan, C, Giambartolomei, C, Hardy, R, Humphries, SE, Hypponen, E, Kivimaki, M, Kuh, D, Kumari, M, Ong, K, Plagnol, V, Power, C, Richards, M, Shah, S, Shah, T, Sofat, R, Talmud, PJ, Wareham, N, Warren, H, Whittaker, JC, Wong, A, Zabaneh, D, Davey Smith, G, Wells, JC, Leon, DA, Holmes, MV & Casas, JP 2016, 'Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis', International journal of epidemiology, vol. 45, no. 6, pp. 1927-1937. https://doi.org/10.1093/ije/dyv074

TY - JOUR

T1 - Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis

AU - Nüesch, Eveline

AU - Dale, Caroline

AU - Palmer, Tom M.

AU - White, Jon

AU - Keating, Brendan J.

AU - van Iperen, Erik Pa

AU - Goel, Anuj

AU - Padmanabhan, Sandosh

AU - Asselbergs, Folkert W.

AU - Verschuren, W. M.

AU - Wijmenga, C.

AU - van der Schouw, Y. T.

AU - Onland-Moret, N. C.

AU - Lange, Leslie A.

AU - Hovingh, G. K.

AU - Sivapalaratnam, Suthesh

AU - Morris, Richard W.

AU - Whincup, Peter H.

AU - Wannamethe, Goya S.

AU - Gaunt, Tom R.

AU - Ebrahim, Shah

AU - Steel, Laura

AU - Nair, Nikhil

AU - Reiner, Alexander P.

AU - Kooperberg, Charles

AU - Wilson, James F.

AU - Bolton, Jennifer L.

AU - McLachlan, Stela

AU - Price, Jacqueline F.

AU - Strachan, Mark Wj

AU - Robertson, Christine M.

AU - Kleber, Marcus E.

AU - Delgado, Graciela

AU - März, Winfried

AU - Melander, Olle

AU - Dominiczak, Anna F.

AU - Farrall, Martin

AU - Watkins, Hugh

AU - Leusink, Maarten

AU - Maitland-van der Zee, Anke H.

AU - de Groot, Mark Ch

AU - Dudbridge, Frank

AU - Hingorani, Aroon

AU - Ben-Shlomo, Yoav

AU - Lawlor, Debbie A.

AU - Amuzu, A.

AU - Caufield, M.

AU - Cavadino, A.

AU - Cooper, J.

AU - Davies, T. L.

AU - Drenos, F.

AU - Engmann, J.

AU - Finan, C.

AU - Giambartolomei, C.

AU - Hardy, R.

AU - Humphries, S. E.

AU - Hypponen, E.

AU - Kivimaki, M.

AU - Kuh, D.

AU - Kumari, M.

AU - Ong, K.

AU - Plagnol, V.

AU - Power, C.

AU - Richards, M.

AU - Shah, S.

AU - Shah, T.

AU - Sofat, R.

AU - Talmud, P. J.

AU - Wareham, N.

AU - Warren, H.

AU - Whittaker, J. C.

AU - Wong, A.

AU - Zabaneh, D.

AU - Davey Smith, George

AU - Wells, Jonathan C.

AU - Leon, David A.

AU - Holmes, Michael V.

AU - Casas, Juan P.

PY - 2016

Y1 - 2016

N2 - We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index ( P < 0.001), triglycerides ( P < 0.001), non high-density (non-HDL) cholesterol ( P < 0.001), C-reactive protein ( P = 0.042), and systolic blood pressure ( P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity ( P < 0.001 for both). Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure

AB - We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index ( P < 0.001), triglycerides ( P < 0.001), non high-density (non-HDL) cholesterol ( P < 0.001), C-reactive protein ( P = 0.042), and systolic blood pressure ( P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity ( P < 0.001 for both). Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure

U2 - https://doi.org/10.1093/ije/dyv074

DO - https://doi.org/10.1093/ije/dyv074

M3 - Article

C2 - 25979724

SN - 0300-5771

VL - 45

SP - 1927

EP - 1937

JO - International journal of epidemiology

JF - International journal of epidemiology

IS - 6

ER -