title: Causal associations of tobacco smoking with cardiovascular risk factors: a Mendelian randomization analysis of the HUNT Study in Norway.
abstract: BACKGROUND
  Tobacco smoking has been associated with cardiovascular risk factors including adverse serum lipid levels, central obesity and higher resting heart rate, but lower blood pressure and body mass index (BMI). We used a Mendelian randomization approach to study whether these associations may be causal. If smoking affects cardiovascular risk factors then rs1051730 T alleles, predictors of increased smoking quantity, should be associated with cardiovascular risk factors among smokers, but not among never smokers.
  
  
  METHODS
  Among 56,625 participants of a population-based study, we estimated associations of rs1051730 T alleles with cardiovascular risk factors and examined whether the associations differed by smoking status.
  
  
  RESULTS
  Rs1051730 T alleles were associated with lower BMI and waist and hip circumferences and higher resting heart rate and estimated glomerular filtration rate (eGFR), and the associations were strongest among current smokers (P interaction 5×10(-9) to 0.01). Rs1051730 T alleles were associated with lower systolic blood pressure and pulse pressure and higher HDL cholesterol concentrations, but these associations did not robustly differ by smoking status. There were no convincing associations of rs1051730 T alleles with waist-hip ratio, diastolic blood pressure and non-fasting serum concentrations of non-HDL cholesterol, triglycerides, glucose and C-reactive protein.
  
  
  CONCLUSIONS
  This Mendelian randomization analysis provides evidence that smoking may cause lower BMI and waist and hip circumferences and higher resting heart rate and eGFR. The findings further suggest that smoking is not a major determinant of waist-hip ratio or adverse blood pressure, serum lipid or glucose levels.
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK, Department of Cancer Research and Molecular Medicine and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK, Department of Cancer Research and Molecular Medicine and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway bjorn.o.asvold@ntnu.no.
authors.forename: Bjørn O
authors.initials: BO
authors.lastname: Åsvold
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK, Department of Cancer Research and Molecular Medicine and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Johan H
authors.initials: JH
authors.lastname: Bjørngaard
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK, Department of Cancer Research and Molecular Medicine and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: David
authors.initials: D
authors.lastname: Carslake
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK, Department of Cancer Research and Molecular Medicine and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Maiken E
authors.initials: ME
authors.lastname: Gabrielsen
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK, Department of Cancer Research and Molecular Medicine and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Frank
authors.initials: F
authors.lastname: Skorpen
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK, Department of Cancer Research and Molecular Medicine and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.affiliation: Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK, Department of Cancer Research and Molecular Medicine and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Pål R
authors.initials: PR
authors.lastname: Romundstad
mesh_terms: D000483:Alleles; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000235:genetics; D015984:Causality; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D057182:Mendelian Randomization Analysis; D009664:Norway / Q000453:epidemiology; D011159:Population Surveillance; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology* / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D049629:Waist-Hip Ratio
chemical_list: D008055:Lipids; D014280:Triglycerides
keywords: Smoking; blood pressure; body mass index; cholesterol; glomerular filtration rate; heart rate