Search

Background: Increasing evidence suggests that smoking influences mental health negatively. This study investigated whether high tobacco consumption is causally related to psychological distress in a Mendelian randomization design, using a variant in the nicotine acetylcholine receptor gene CHRNA3-known to influence individual tobacco consumption-as instrumental variable for tobacco consumption.Methods: Data from 90 108 participants in the Copenhagen General Population Study was used. Exposures included self-reported cigarettes/day and pack years and the CHRNA3 rs1051730 genotype as instrumental variable for tobacco consumption. Three dimensions of psychological distress were studied: Stress, fatigue, and hopelessness. Analyses with the CHRNA3 genotype were stratified by smoking status.Results: Self-reported amount of smoking was associated with all three dimensions of psychological distress. For instance among participants smoking 30 cigarettes/day or more, the odds ratio (OR) for stress was 1.67 (95% confidence interval [CI] 1.47-1.89) compared to never-smokers. Corresponding ORs for fatigue and hopelessness were 2.18 (95% CI 1.92-2.47) and 3.08 (95% CI 2.62-3.62). Among current smokers, homozygotes and heterozygotes for the CHRNA3 genotype had higher tobacco consumption than noncarriers. Nevertheless, the CHRNA3 genotype was not associated with psychological distress neither in current nor in former or never-smokers. For instance among current smokers, the OR for stress was 1.02 (95% CI 0.91-1.15) among homozygotes compared to noncarriers of the CHRNA3 genotype.Conclusions: Though a strong association between tobacco consumption and psychological distress was found, there was no clear evidence that high tobacco consumption was causally related to psychological distress.Implications: Smoking is associated with several mental health outcomes and smoking cessation is associated with improved mental health. Causality in the association between smoking and mental health is difficult to establish using observational data. Using a genotype known to influence tobacco consumption as instrumental variable for amount of smoking, we found no clear evidence of a direct causal path between high tobacco consumption and psychological distress. Whatever causes the strong association between tobacco consumption and psychological distress, the co-occurrence is important to consider both in interventions for smoking prevention and cessation. [ABSTRACT FROM AUTHOR]

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/m² (0.01; 0.02) higher body mass index, 0.10cm (0.07; 0.12) higher waist circumference and 0.02cm (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/m² (0.33; 0.13) lower body mass index, 0.32cm (0.74; 0.003) lower waist circumference and 0.45cm (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. [ABSTRACT FROM AUTHOR]

Introduction: Observational studies have found lower concentrations of plasma bilirubin in current smokers compared with former and never smokers. However, whether there is a causal relationship between smoking and bilirubin is unknown. In a Mendelian randomization analysis, we tested the hypothesis that higher tobacco consumption is causally associated with lower concentrations of plasma bilirubin.Methods: We genotyped 103 557 individuals aged 20-100 years from the Copenhagen General Population Study for the CHRNA3 rs1051730 genotype, known to be associated with higher tobacco consumption. Tobacco consumption was defined as daily and cumulative tobacco consumption.Results: In observational multivariable-adjusted analyses, a 10 g/day higher daily tobacco consumption was associated with a 0.28 µmol/L (95% confidence interval = 0.20 to 0.35) lower concentration of plasma bilirubin in current smokers, and a 10 pack-year higher cumulative tobacco consumption was associated with a 0.19 µmol/L (0.17 to 0.21) lower concentration of plasma bilirubin in former and current smokers. Using the CHRNA3 rs1051730 genotype as a proxy for daily and cumulative tobacco consumption, the difference in plasma bilirubin per T-allele was -0.12 µmol/L (-0.23 to -0.002) in current smokers and -0.09 µmol/L (-0.15 to -0.01) in current and former smokers combined. Furthermore, observationally bilirubin concentrations increased with time from smoking cessation in former smokers.Conclusion: Higher daily and cumulative tobacco consumption were associated with lower concentrations of plasma bilirubin in observational and genetic analyses, suggesting that the association is causal.Implications: Our results are compatible with two possible interpretations of previous observational studies, either that bilirubin is a mediator of smoking-induced respiratory disease or that the association between plasma bilirubin and respiratory disease stems from residual confounding because of smoking. Future studies should examine whether bilirubin is a causal risk factor for respiratory disease, or merely a marker of smoking status. [ABSTRACT FROM AUTHOR]

Introduction: Smoking is associated with systemic and local inflammation in the lungs. Furthermore, in chronic obstructive pulmonary disease, which is often caused by smoking, there is often systemic inflammation that is linked to lung function impairment. However, the causal pathways linking smoking, systemic inflammation, and airflow limitation are still unknown. We tested whether higher tobacco consumption is associated with higher systemic inflammation, observationally and genetically and whether genetically higher systemic inflammation is associated with airflow limitation.Methods: We included 98 085 individuals aged 20-100 years from the Copenhagen General Population Study; 36589 were former smokers and 16172 were current smokers. CHRNA3 rs1051730 genotype was used as a proxy for higher tobacco consumption and the IL6R rs2228145 genotype was used for higher systemic inflammation. Airflow limitation was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <70%.Results: Difference in plasma level of C-reactive protein was 4.8% (95% CI = 4.4% to 5.2%) per 10 pack-year increase and 1.6% (95% CI = 0.4% to 2.8%) per T allele. Corresponding differences were 1.2% (95% CI = 1.1% to 1.3%) and 0.5% (95% CI = 0.3% to 0.8%) for fibrinogen, 1.2% (95% CI = 1.2% to 1.3%) and 0.7% (95% CI = 0.5% to 1.0%) for α1-antitrypsin, 2.0% (95% CI = 1.8% to 2.1%) and 0.7% (95% CI = 0.4% to 1.1%) for leukocytes, 1.9% (95% CI = 1.8% to 2.1%) and 0.8% (95% CI = 0.4% to 1.2%) for neutrophils, and 0.8% (95% CI = 0.7% to 1.0%) and 0.4% (95% CI = 0.1% to 0.7%) for thrombocytes. The differences in these levels were lower for former smokers compared with current smokers. The IL6R rs2228145 genotype was associated with higher plasma acute-phase reactants but not with airflow limitation. Compared with the C/C genotype, the odds ratio for airflow limitation was 0.95 (95% CI = 0.89 to 1.02) for A/C genotype and 0.94 (95% CI = 0.87 to 1.01) for A/A genotype.Conclusions: Higher tobacco consumption is associated with higher systemic inflammation both genetically and observationally, whereas systemic inflammation was not associated with airflow limitation genetically.Implications: The association between higher tobacco consumption and higher systemic inflammation may be causal, and the association is stronger among current smokers compared to former smokers, indicating that smoking cessation may reduce the effects of smoking on systemic inflammation. Systemic inflammation does not seem to be a causal driver in development of airflow limitation. These findings can help to understand the pathogenic effects of smoking and the interplay between smoking, systemic inflammation, and airflow limitation and hence development and progression of chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Background. Human immunodeficiency virus-infected individuals have increased risk of myocardial infarction (MI); however, the contribution from smoking and potentiating effects of HIV are controversial. Methods. From the Danish HIV Cohort Study and the Copenhagen General Population Study, we identified 3251 HIV-infected individuals and 13 004 population controls matched on age and gender. Data on MI were obtained from the National Hospital Registry and the National Registry of Causes of Death.We calculated adjusted incidence rate ratios (aIRR) for risk of MI and population-attributable fractions (PAF) of MI associated with smoking. Results. In never smokers, HIV was not associated with an increased risk ofMI (aIRR, 1.01; 95% confidence interval [CI], .41-2.54). In previous and current smokers, HIV was associated with a substantially increased risk of MI (aIRR, 1.78; 95% CI, .75-4.24 and aIRR, 2.83; 95% CI, 1.71-4.70). The PAF associated with ever smoking (previous or current) was 72% (95% CI, 55%-82%) for HIV-infected individuals and 24% (95% CI, 3%-40%) for population controls. If all current smokers stopped smoking, 42% (95% CI, 21%-57%) and 21% (95% CI, 12%-28%) of all MIs could potentially be avoided in these 2 populations. Conclusions. Smoking is associated with a higher risk of MI in the HIV-infected population than in the general population. Approximately 3 of 4 MIs among HIV-infected individuals are associated with ever smoking compared with only 1 of 4 MIs among population controls. Smoking cessation could potentially prevent more than 40% of MIs among HIV-infected individuals, and smoking cessation should be a primary focus in modern HIV care. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Among Danish human immunodeficiency virus (HIV) patients, smokers lose more life-years to smoking than to HIV. The excess mortality of smokers is tripled and the population attributable risk of death associated with smoking is doubled among HIV patients compared with the background populationBackground. We assessed mortality attributable to smoking among patients with human immunodeficiency virus (HIV).Methods. We estimated mortality rates (MRs), mortality rate ratios (MRRs), life expectancies, life-years lost, and population-attributable risk of death associated with smoking and with HIV among current and nonsmoking individuals from a population-based, nationwide HIV cohort and a cohort of matched HIV-negative individuals.Results. A total of 2921 HIV patients and 10 642 controls were followed for 14 281 and 45 122 person-years, respectively. All-cause and non-AIDS-related mortality was substantially increased among smoking compared to nonsmoking HIV patients (MRR, 4.4 [95% confidence interval {CI}, 3.0–6.7] and 5.3 [95% CI, 3.2–8.8], respectively). Excess MR per 1000 person-years among current vs nonsmokers was 17.6 (95% CI, 13.3–21.9) for HIV patients and 4.8 (95% CI, 3.2–6.4) for controls. A 35-year-old HIV patient had a median life expectancy of 62.6 years (95% CI, 59.9–64.6) for smokers and 78.4 years (95% CI, 70.8–84.0) for nonsmokers; the numbers of life-years lost in association with smoking and HIV were 12.3 (95% CI, 8.1–16.4) and 5.1 (95% CI, 1.6–8.5). The population-attributable risk of death associated with smoking was 61.5% among HIV patients and 34.2% among controls.Conclusions. In a setting where HIV care is well organized and antiretroviral therapy is free of charge, HIV-infected smokers lose more life-years to smoking than to HIV. The excess mortality of smokers is tripled and the population-attributable risk of death associated with smoking is doubled among HIV patients compared to the background population. [ABSTRACT FROM PUBLISHER]