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 P.A. van Iperen, Anuj Goel, Sandosh Padmanabhan, F. 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 W.J. 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 C.H. de Groot, Frank Dudbridge, Aroon Hingorani, Yoav Ben-Shlomo, Debbie A. Lawlor, A. Amuzu, M. Caufield, A. Cavadino, J. Cooper, T. L. Davies, I. N. Day, 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

Background: 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. Methods: 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. Results: 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). Conclusions: 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 languageEnglish
Article numberdyv074
Pages (from-to)1927-1937
Number of pages11
JournalInternational Journal of Epidemiology
Volume45
Issue number6
DOIs
Publication statusPublished - 1 Dec 2016

ASJC Scopus subject areas

  • Epidemiology

Cite this

Nüesch, E., Dale, C., Palmer, T. M., White, J., Keating, B. J., van Iperen, E. P. A., ... 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. [dyv074]. https://doi.org/10.1093/ije/dyv074