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Int J Epidemiol. 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.

Author information

1
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
2
CTU Bern, Department of Clinical Research and Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
3
Warwick Medical School, University of Warwick, Coventry, UK.
4
Department of Mathematics and Statistics, Lancaster University, Lancaster, UK.
5
UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.
6
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
7
Department of Surgery.
8
Division of Genetics, University of Pennsylvania, Philadelphia.
9
Department of Biostatistics, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
10
Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands.
11
Wellcome Trust Centre for Human Genetics and Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
12
Institute of Cardiovascular and Medical Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
13
Department of Cardiology, Division Heart and Lungs, University Medical Centre Utrecht, Utrecht, The Netherlands.
14
Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK.
15
EPIC-NL, Bilthoven and Utrecht, The Netherlands.
16
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
17
Department of Vascular Medicine, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
18
Department of Primary Care & Population Health, University College London, London, UK.
19
Population Health Research Institute, St George's, University of London, London, UK.
20
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
21
School of Social and Community Medicine, University of Bristol, Bristol, UK.
22
Department of Epidemiology, University of Washington, Seattle, WA, USA / Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
23
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
24
Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
25
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
26
Metabolic Unit, Western General Hospital, Edinburgh, UK.
27
Fifth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
28
Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetolgy, and Rheumatology), Mannheim Medical Faculty, University of Heidelberg, Germany, Synlab Academy, Synlab Services GmbH, Mannheim and Augsburg, Germany, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria.
29
Lund University, Sweden.
30
Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
31
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
32
Department of Epidemiology and Public Health, University College London Medical School, London, UK.
33
UCLEB, London, Edinburgh and Bristol, UK.
34
Childhood Nutrition Research Centre, UCL Institute of Child Health, London, UK.
35
Department of Community Medicine, Arctic University of Norway, UiT.
36
Department of Surgery and Clinical Epidemiology Unit, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
37
Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.

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.

PMID:
25979724
PMCID:
PMC5841831
DOI:
10.1093/ije/dyv074
[Indexed for MEDLINE]
Free PMC Article

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