Publication type
Journal Article
Authors
Publication date
December 15, 2015
Summary:
Objectives: The observed associations between smoking and functional measures at older ages are vulnerable to bias and confounding. Mendelian randomisation (MR) uses genotype as an instrumental variable to estimate unconfounded causal associations. We conducted a meta-analysis of the observational associations and implemented an MR approach using the smoking-related single nucleotide polymorphism rs16969968 to explore their causal nature.
Setting: 9 British cohorts belonging to the HALCyon collaboration.
Participants: Individual participant data on N=26 692 individuals of European ancestry (N from earliest phase analysed per study) of mean ages 50–79 years were available for inclusion in observational meta-analyses of the primary outcomes.
Primary outcomes: Physical capability, cognitive capability and cognitive decline. The smoking exposures were cigarettes per day, current versus ex-smoker, current versus never smoker and ever versus never smoker.
Results: In observational analyses current and ever smoking were generally associated with poorer physical and cognitive capability. For example, current smokers had a general fluid cognition score which was 0.17 z-score units (95% CI −0.221 to −0.124) lower than ex-smokers in cross-sectional analyses. Current smokers had a walk speed which was 0.25 z-score units lower than never smokers (95% CI −0.338 to −0.170). An MR instrumental variable approach for current versus ex-smoker and number of cigarettes smoked per day produced CIs which neither confirmed nor refuted the observational estimates. The number of genetic associations stratified by smoking status were consistent with type I error.
Conclusions: Our observational analysis supports the hypothesis that smoking is detrimental to physical and cognitive capability. Further studies are needed for a suitably powered MR approach.
Published in
BMJ Open
Volume
Volume: 5
DOI
http://dx.doi.org/10.1136/bmjopen-2015-008393
ISSN
20446055
Subjects
Notes
Open Acess article
This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/
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