Does High Tobacco Consumption Cause Psychological Distress? A Mendelian Randomization Study.
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.



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.



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.



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.



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.
National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark; lse@niph.dk.
Lise S
LS
Skov-Ettrup
Department of Clinical Biochemistry and The Copenhagen General Population Study, Copenhagen University Hospital, Herlev, Denmark.
Børge G
BG
Nordestgaard
National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
Christina B
CB
Petersen
National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
Janne S
JS
Tolstrup
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D017831:Diagnosis, Dual (Psychiatry); D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis / Q000379:methods; D008875:Middle Aged; D016017:Odds Ratio; D011978:Receptors, Nicotinic / Q000235:genetics; D012907:Smoking / Q000453:epidemiology / Q000235:genetics / Q000523:psychology*; D016540:Smoking Cessation; D013315:Stress, Psychological / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000523:psychology; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000235:genetics / Q000523:psychology*; D055815:Young Adult
D011978:Receptors, Nicotinic