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. 2016 Dec 1;45(6):1927-1937.
doi: 10.1093/ije/dyv074.

Adult Height, Coronary Heart Disease and Stroke: A Multi-Locus Mendelian Randomization Meta-Analysis

Eveline Nüesch  1   2 Caroline Dale  1 Tom M Palmer  3   4 Jon White  5 Brendan J Keating  6   7   8 Erik Pa van Iperen  9   10 Anuj Goel  11 Sandosh Padmanabhan  12 Folkert W Asselbergs  13   10   14 EPIC-Netherland InvestigatorsW M VerschurenC WijmengaY T Van der SchouwN C Onland-Moret  15 Leslie A Lange  16 G K Hovingh  17 Suthesh Sivapalaratnam  17 Richard W Morris  18 Peter H Whincup  19 Goya S Wannamethe  18 Tom R Gaunt  20   21 Shah Ebrahim  1 Laura Steel  6 Nikhil Nair  6 Alexander P Reiner  22 Charles Kooperberg  23 James F Wilson  24   25 Jennifer L Bolton  24 Stela McLachlan  24 Jacqueline F Price  24 Mark Wj Strachan  26 Christine M Robertson  24 Marcus E Kleber  27 Graciela Delgado  27 Winfried März  28 Olle Melander  29 Anna F Dominiczak  12 Martin Farrall  11 Hugh Watkins  11 Maarten Leusink  30   31 Anke H Maitland-van der Zee  30 Mark Ch de Groot  30   31 Frank Dudbridge  1 Aroon Hingorani  32 Yoav Ben-Shlomo  21 Debbie A Lawlor  20   21 UCLEB InvestigatorsA AmuzuM CaufieldA CavadinoJ CooperT L DaviesIN DayF DrenosJ EngmannC FinanC GiambartolomeiR HardyS E HumphriesE HypponenM KivimakiD KuhM KumariK OngV PlagnolC PowerM RichardsS ShahT ShahR SofatP J TalmudN WarehamH WarrenJ C WhittakerA WongD Zabaneh  33 George Davey Smith  20   21 Jonathan C Wells  34 David A Leon  1   35 Michael V Holmes  14   36   37 Juan P Casas  1   14
Free PMC article

Adult Height, Coronary Heart Disease and Stroke: A Multi-Locus Mendelian Randomization Meta-Analysis

Eveline Nüesch et al. Int J Epidemiol. .
Free PMC article


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.


Figure 1.
Figure 1.
Meta-analysis pooled estimates for the association between deciles of the allele score and adult height. Presented are pooled differences in mean adult height with corresponding 95% confidence intervals as compared with the 5th decile, derived from fixed-effect meta-analysis. N, numbers analysed in each decile.
Figure 2.
Figure 2.
Meta-analysis pooled causal effects for a 6.5-cm increase in adult height on the risk of cardiovascular disease. Odds ratios and corresponding 95% confidence intervals (CI) are estimated from fixed-effect meta-analysis of instrumental variable (IV) estimates from individual studies. Hazard ratios are taken from estimates published by the Emerging Risk Factors Collaboration (ERFC). Effect estimates are per 6.5 cm increase in adult height. An estimate below 1 indicates that increasing adult height decreases the risk of cardiovascular events.

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