Abstract

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.

Eirini Marouli et al. use Mendelian randomisation analyses to investigate the causal relationship between adult height, coronary artery disease (CAD) and type 2 diabetes (T2D) in the UK Biobank. They find that height has a causal effect on CAD, which is mediated by lung function, while there is no direct effect on the risk of T2D.

Details

Title
Mendelian randomisation analyses find pulmonary factors mediate the effect of height on coronary artery disease
Author
Marouli Eirini 1 ; Del Greco M Fabiola 2 ; Astley, Christina M 3 ; Yang, Jian 4   VIAFID ORCID Logo  ; Ahmad Shafqat 5 ; Berndt, Sonja I 6 ; Caulfield, Mark J 7   VIAFID ORCID Logo  ; Evangelou Evangelos 8   VIAFID ORCID Logo  ; McKnight, Barbara 9 ; Medina-Gomez, Carolina 10   VIAFID ORCID Logo  ; van Vliet-Ostaptchouk Jana V 11   VIAFID ORCID Logo  ; Warren, Helen R 7 ; Zhu, Zhihong 12 ; Hirschhorn, Joel N 3 ; Loos Ruth J F 13   VIAFID ORCID Logo  ; Kutalik Zoltan 14   VIAFID ORCID Logo  ; Deloukas Panos 15   VIAFID ORCID Logo 

1  Queen Mary University of London, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133); Queen Mary University of London, Centre for Genomic Health, Life Sciences, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133) 
2  Affiliated Institute of the University of Lubeck, Institute for Biomedicine, Eurac Research, Bolzano, Italy (GRID:grid.4868.2) 
3  Boston Children’s Hospital, Boston, USA (GRID:grid.2515.3) (ISNI:0000 0004 0378 8438); Broad Institute of Harvard and MIT, Cambridge, USA (GRID:grid.66859.34) 
4  University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); The University of Queensland, Queensland Brain Institute, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
5  Harvard University, Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Brigham and Women’s Hospital, Division of Preventive Medicine, Harvard Medical School, Department of Medicine, Boston, USA (GRID:grid.62560.37) (ISNI:0000 0004 0378 8294); Uppsala University, Department of Medical Sciences, Molecular Epidemiology, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457) 
6  Department of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
7  Queen Mary University of London, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133); Queen Mary University of London, National Institute for Health Research, Barts Cardiovascular Biomedical Research Center, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133) 
8  Imperial College London, Department of Epidemiology and Biostatistics, School of Public Health, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); University of Ioannina Medical School, Department of Hygiene and Epidemiology, Ioannina, Greece (GRID:grid.9594.1) (ISNI:0000 0001 2108 7481) 
9  University of Washington, Department of Biostatistics, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
10  Erasmus Medical Center, Department of Internal Medicine, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X); Erasmus Medical Center, Department of Epidemiology, Rotterdam, The Netherlands (GRID:grid.5645.2) (ISNI:000000040459992X) 
11  University of Groningen, University Medical Center Groningen, Department of Endocrinology, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598) 
12  University of Queensland, Institute for Molecular Bioscience, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
13  The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
14  Lausanne University Hospital, Institute of Social and Preventive Medicine, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); Swiss Institute of Bioinformatics, Lausanne, Switzerland (GRID:grid.419765.8) (ISNI:0000 0001 2223 3006) 
15  Queen Mary University of London, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133); Queen Mary University of London, Centre for Genomic Health, Life Sciences, London, UK (GRID:grid.4868.2) (ISNI:0000 0001 2171 1133); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia (GRID:grid.412125.1) (ISNI:0000 0001 0619 1117) 
Publication year
2019
Publication date
2019
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-019-0361-2
ProQuest document ID
2383000816
Copyright
© The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.