title: Effect of smoking on physical and cognitive capability in later life: a multicohort study using observational and genetic approaches.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  9 British cohorts belonging to the HALCyon collaboration.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Teri-Louise
authors.initials: TL
authors.lastname: North
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK Division of Health Sciences, Warwick Medical School, University of Warwick, Warwick, UK Department of Mathematics and Statistics, Lancaster University, Lancaster, UK.
authors.forename: Tom M
authors.initials: TM
authors.lastname: Palmer
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lewis
authors.affiliation: MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Cooper
authors.affiliation: Population, Policy and Practice, UCL Institute of Child Health, University College London, London, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Power
authors.affiliation: Department of Psychology, University of Edinburgh, Edinburgh, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Pattie
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.affiliation: Department of Psychology, University of Edinburgh, Edinburgh, UK Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK University of Bristol/University Hospitals Bristol NHS Foundation Trust National Institute for Health Research Bristol Nutrition Biomedical Research Unit, University of Bristol, Bristol, UK.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
authors.forename: Avan
authors.initials: A
authors.lastname: Aihie Sayer
authors.affiliation: ISER, University of Essex, Essex, UK Department of Epidemiology and Public Health, UCL, London, UK.
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK National Institute for Health Research Nutrition Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK National Institute for Health Research Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Department of Epidemiology and Public Health, UCL, London, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.affiliation: MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Kuh
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Ian N M
authors.initials: IN
authors.lastname: Day
mesh_terms: D003071:Cognition / Q000187:drug effects*; D006801:Humans; D057182:Mendelian Randomization Analysis; D064887:Observational Studies as Topic; D010809:Physical Fitness; D011978:Receptors, Nicotinic / Q000235:genetics; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology / Q000235:genetics; D006113:United Kingdom; D044465:White People / Q000235:genetics*
chemical_list: D011978:Receptors, Nicotinic
keywords: EPIDEMIOLOGY; GENETICS; GERIATRIC MEDICINE