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

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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. / Rode, Line; Bojesen, Stig E; Weischer, Maren; Nordestgaard, Børge G.

In: International Journal of Epidemiology, Vol. 43, No. 5, 2014, p. 1473-1483.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Rode, L, Bojesen, SE, Weischer, M & Nordestgaard, BG 2014, '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', International Journal of Epidemiology, vol. 43, no. 5, pp. 1473-1483. https://doi.org/10.1093/ije/dyu119

APA

Rode, L., Bojesen, S. E., Weischer, M., & Nordestgaard, B. G. (2014). 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. International Journal of Epidemiology, 43(5), 1473-1483. https://doi.org/10.1093/ije/dyu119

Vancouver

Rode L, Bojesen SE, Weischer M, Nordestgaard BG. 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. International Journal of Epidemiology. 2014;43(5):1473-1483. https://doi.org/10.1093/ije/dyu119

Author

Rode, Line ; Bojesen, Stig E ; Weischer, Maren ; Nordestgaard, Børge G. / 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. In: International Journal of Epidemiology. 2014 ; Vol. 43, No. 5. pp. 1473-1483.

Bibtex

@article{abf9adb1a7824cdb9b5e1d68fc02f632,
title = "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",
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.",
keywords = "Denmark, Female, Follow-Up Studies, Genotype, Humans, Incidence, Male, Mendelian Randomization Analysis, Mortality, Multivariate Analysis, Polymorphism, Genetic, Risk Factors, Smoking, Telomere, Tobacco Use Disorder",
author = "Line Rode and Bojesen, {Stig E} and Maren Weischer and Nordestgaard, {B{\o}rge G}",
note = "{\circledC} The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.",
year = "2014",
doi = "10.1093/ije/dyu119",
language = "English",
volume = "43",
pages = "1473--1483",
journal = "International Journal of Epidemiology",
issn = "0300-5771",
publisher = "Oxford University Press",
number = "5",

}

RIS

TY - JOUR

T1 - 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

T2 - a Mendelian randomization study

AU - Rode, Line

AU - Bojesen, Stig E

AU - Weischer, Maren

AU - Nordestgaard, Børge G

N1 - © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

KW - Denmark

KW - Female

KW - Follow-Up Studies

KW - Genotype

KW - Humans

KW - Incidence

KW - Male

KW - Mendelian Randomization Analysis

KW - Mortality

KW - Multivariate Analysis

KW - Polymorphism, Genetic

KW - Risk Factors

KW - Smoking

KW - Telomere

KW - Tobacco Use Disorder

U2 - 10.1093/ije/dyu119

DO - 10.1093/ije/dyu119

M3 - Journal article

C2 - 24906368

VL - 43

SP - 1473

EP - 1483

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

SN - 0300-5771

IS - 5

ER -

ID: 138271384