1. High tobacco consumption is causally associated with increased all-cause mortality in a general population sample of 55,568 individuals, but not with short telomeres: a Mendelian randomization study.
- Author
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Rode L, Bojesen SE, Weischer M, and Nordestgaard BG
- Subjects
- Denmark epidemiology, Female, Follow-Up Studies, Genotype, Humans, Incidence, Male, Multivariate Analysis, Polymorphism, Genetic, Risk Factors, Smoking mortality, Tobacco Use Disorder mortality, Mendelian Randomization Analysis, Mortality, Smoking genetics, Telomere genetics, Tobacco Use Disorder genetics
- Abstract
Background: High cumulative tobacco consumption is associated with short telomeres and with increased all-cause mortality. We tested the hypothesis that high tobacco consumption is causally associated with short telomeres and with increased all-cause mortality., Methods: We studied 55,568 individuals including 32,823 ever smokers from the Danish general population, of whom 3430 died during 10 years of follow-up. All had telomere length measured, detailed information on smoking history, and CHRNA3 rs1051730 genotype, which is associated with tobacco consumption, determined. In a Mendelian randomization study, we conducted observational, genetic, and mediation analyses., Results: First, tobacco consumption was 21.1 pack-years in non-carriers, 22.8 in heterozygotes and 24.8 in homozygotes (P-trend<0.001). Second, the observational multivariable adjusted hazard ratio for all-cause mortality was 1.12 [95% confidence interval (CI): 1.09, 1.15] per doubling in tobacco consumption. In Mendelian randomization analysis, the hazard ratio was 1.08 (1.02, 1.14) per minor CHRNA3 allele in ever smokers. Third, in observational analysis telomeres shortened with -13 base pairs (-18, -8) per doubling in tobacco consumption. In Mendelian randomization analysis, the estimate was +3 base pairs (-10, +15) per minor CHRNA3 allele. Finally, individuals with the shortest vs longest telomeres had a multivariable adjusted hazard ratio of 1.30 (1.13, 1.50) for all-cause mortality; however, in mediation analysis short telomeres explained only +0.4% (-3.5%, +4.3%) of the association between high tobacco consumption and increased all-cause mortality., Conclusions: High tobacco consumption is causally associated with increased all-cause mortality. High cumulative tobacco consumption is associated with short telomeres observationally, but there is no clear genetic association., (© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)
- Published
- 2014
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