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Commun Biol. 2019 Mar 27;2:119. doi: 10.1038/s42003-019-0361-2. eCollection 2019.

Mendelian randomisation analyses find pulmonary factors mediate the effect of height on coronary artery disease.

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1William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ UK.
2Centre for Genomic Health, Life Sciences, Queen Mary University of London, London, EC1M 6BQ UK.
Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, 39100 Italy.
4Boston Children's Hospital, Boston, MA 02115 USA.
5Broad Institute of Harvard and MIT, Cambridge, MA 02142 USA.
6Institute for Molecular Bioscience, University of Queensland, Brisbane, 4072 QLD Australia.
7Queensland Brain Institute, The University of Queensland, Brisbane, 4072 QLD Australia.
8Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115 USA.
9Division of Preventive Medicine, Harvard Medical School, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02215 USA.
10Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, 751 41 Sweden.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892 USA.
12National Institute for Health Research, Barts Cardiovascular Biomedical Research Center, Queen Mary University of London, London, EC1M 6BQ UK.
13Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, W2 1PG UK.
14Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110 Greece.
15Department of Biostatistics, University of Washington, Seattle, WA 98101 USA.
16Department of Internal Medicine, Erasmus Medical Center, Rotterdam, 3015 GE The Netherlands.
17Department of Epidemiology, Erasmus Medical Center, Rotterdam, 3015 GE The Netherlands.
18Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, 9713 GZ The Netherlands.
19The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA.
20Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, 1010 Switzerland.
21Swiss Institute of Bioinformatics, Lausanne, 1015 Switzerland.
22Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, 21589 Saudi Arabia.


There is evidence that lower height is associated with a higher risk of coronary artery disease (CAD) and increased risk of type 2 diabetes (T2D). It is not clear though whether these associations are causal, direct or mediated by other factors. Here we show that one standard deviation higher genetically determined height (~6.5 cm) is causally associated with a 16% decrease in CAD risk (OR = 0.84, 95% CI 0.80-0.87). This causal association remains after performing sensitivity analyses relaxing pleiotropy assumptions. The causal effect of height on CAD risk is reduced by 1-3% after adjustment for potential mediators (lipids, blood pressure, glycaemic traits, body mass index, socio-economic status). In contrast, our data suggest that lung function (measured by forced expiratory volume [FEV1] and forced vital capacity [FVC]) is a mediator of the effect of height on CAD. We observe no direct causal effect of height on the risk of T2D.

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