title: High tobacco consumption lowers body weight: a Mendelian randomization study of the Copenhagen General Population Study.
abstract: BACKGROUND
  Conflicting evidence has been found regarding the association between high tobacco consumption and body weight among smokers. We tested the hypothesis that high tobacco consumption is causally associated with low body weight.
  
  
  METHODS
  We conducted a Mendelian randomization study with a genetic variant in CHRNA3 (rs1051730) as proxy for high tobacco consumption. The cohort consisted of 80,342 participants from the Copenhagen General Population Study, with details on body weight, smoking habits and CHRNA3 genotype, including 15,220 current smokers.
  
  
  RESULTS
  In observational analyses, high tobacco consumption was associated with high body weight, body mass index, waist circumference, hip circumference and waist-hip ratio. In multivariable adjusted models a 1-cigarette/day higher tobacco consumption was associated with 0.05 kg (95% confidence interval 0.02; 0.08) higher body weight, 0.02 kg/m(2) (0.01; 0.02) higher body mass index, 0.10 cm (0.07; 0.12) higher waist circumference and 0.02 cm (0.001; 0.03) higher hip circumference. In contrast, the per-allele increase inCHRNA3 rs1051730 associated with high tobacco consumption was associated with 0.59 kg (0.96; 0.22) lower body weight, 0.23 kg/m(2) (0.33; 0.13) lower body mass index, 0.32 cm (0.74; 0.003) lower waist circumference and 0.45 cm (0.66; 0.24) lower hip circumference. No association was found between tobacco consumption and waist-hip ratio in genetic analysis, or among CHRNA3 genotype and any of the outcome variables in former or never smokers.
  
  
  CONCLUSIONS
  High tobacco consumption causes lower body weight among current smokers. However, smoking does not seem to affect body shape or fat distribution causally. The lack of association between CHRNA3 genotype and body weight among former smokers and never smokers favours smoking as the causal factor for the observed associations.
authors.affiliation: Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulrik C
authors.initials: UC
authors.lastname: Winsløw
authors.affiliation: Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Line
authors.initials: L
authors.lastname: Rode
authors.affiliation: Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Boerge.Nordestgaard@regionh.dk.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D010641:Phenotype; D011978:Receptors, Nicotinic / Q000235:genetics; D012907:Smoking / Q000453:epidemiology / Q000235:genetics*; D064424:Tobacco Use / Q000453:epidemiology; D049629:Waist-Hip Ratio; D015430:Weight Gain / Q000235:genetics / Q000502:physiology; D015431:Weight Loss / Q000235:genetics* / Q000502:physiology; D055815:Young Adult
chemical_list: D011978:Receptors, Nicotinic
keywords: Mendelian randomization; Smoking; body weight; fat distribution; general population; genetic variants