Lung function and cardiovascular disease: a two-sample Mendelian randomisation study

Daniel H Higbee, Raquel Granell, Eleanor C M Sanderson, George Davey Smith, James Dodd*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

24 Citations (Scopus)
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Observational studies suggest an association between reduced lung function and risk of coronary artery disease and ischaemic stroke, independent of shared cardiovascular risk factors such as cigarette smoking. We use the latest genetic epidemiological methods to determine if impaired lung function is causally associated with an increased risk of cardiovascular disease.
Methods and Findings
Mendelian Randomization uses genetic variants as instrumental variables to investigate causation. Preliminary analysis used two sample Mendelian Randomization with lung function single nucleotide polymorphisms. To avoid collider bias the main analysis used single nucleotide polymorphisms for lung function identified from UKBiobank in a Multivariable Mendelian Randomization model conditioning for height, body mass index and smoking.
Multivariable Mendelian Randomization shows strong evidence that reduced FVC causes increased risk of coronary artery disease, Odds Ratio:1·32 (1·19-1·46) per Standard Deviation. Reduced FEV1 is unlikely to be cause increased risk of coronary artery disease as evidence of its effect becomes weak after conditioning for height 1·08 (0·89, 1·30). There is weak evidence that reduced lung function increases risk of ischaemic stroke.
There is strong evidence that reduced FVC is independently and causally associated with coronary artery disease. Although the mechanism remains unclear, FVC could be taken into consideration when assessing cardiovascular risk and considered a potential target for reducing cardiovascular events. FEV1 and airflow obstruction do not appear to cause increased cardiovascular events, confounding and collider bias may explain previous findings of a causal association.
Original languageEnglish
Article number2003196
JournalEuropean Respiratory Journal
Issue number3
Early online date11 Feb 2021
Publication statusPublished - Sept 2021

Bibliographical note

Funding Information:
Support statement: This work was supported by the Medical Research Council and the University of Bristol (MC_UU_00011/1); MRC CARP Fellowship. Funding information for this article has been deposited with the Crossref Funder Registry.

Publisher Copyright:
© 2021 European Respiratory Society. All rights reserved.


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