Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium

Abstract

ObjectivesTo investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach.DesignMendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress.ParticipantsCurrent, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).Primary outcome measuresBinary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis.ResultsThe analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers.ConclusionsFindings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.

Phenome-Wide Association Study for Alcohol and Nicotine Risk Alleles in 26394 Women

“…Tobacco use, abuse, and dependence frequently co-occur with several psychiatric traits and disorders (Picciotto and Kenny, 2013) especially with depression and anxiety (Morozova et al, 2015). However, results from a recent Mendelian randomization analysis did not support a causal role of smoking heaviness towards the development of depression and anxiety (Taylor et al, 2014). In our study, individuals with a smoking-related risk allele tended to report more frequently that 'most people lie to get ahead' than those without the risk allele.…”

The causal role of smoking on the risk of hip or knee replacement due to primary osteoarthritis: a Mendelian randomisation analysis of the HUNT study

“…Each additional T allele at the rs1051730 SNP is associated with an increase in the number of cigarettes smoked per day and increased cotinine levels, a metabolite of nicotine, among current smokers 14 . The rs1051730 SNP has been used as an instrument for smoking intensity in former Mendelian randomisation studies investigating the causal effect of cigarette smoking on body mass index (BMI), anxiety and depression and cardiovascular risk factors [15][16][17][18][19] .…”

The possible role of maternal bonding style and CHRNB2 gene polymorphisms in nicotine dependence and related depressive phenotype

“…In another genetic study, depression and anxiety were investigated in never, former, current and ever smokers in association with two SNPs in the CHRNA4-A3-B4 gene cluster. There were no significant associations between polymorhpisms and depressive phenotypes in smokers (Taylor et al, 2014). However, tag SNPs showed a moderate effect on anxiety and psychological distress in never smokers (Taylor et al, 2014).…”

“…There were no significant associations between polymorhpisms and depressive phenotypes in smokers (Taylor et al, 2014). However, tag SNPs showed a moderate effect on anxiety and psychological distress in never smokers (Taylor et al, 2014).…”