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Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study.

ABSTRACT: BACKGROUND:Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS). METHODS:We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium. RESULTS:There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67-3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71-2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (? = 0.091, 95% CI 0.027-0.155, p = 0.005) but evidence was mixed for schizophrenia (? = 0.022, 95% CI 0.005-0.038, p = 0.009) with very weak evidence for an effect on smoking initiation. CONCLUSIONS:These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.

SUBMITTER: Wootton RE

PROVIDER: S-EPMC7610182 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study.

Wootton Robyn E RE Richmond Rebecca C RC Stuijfzand Bobby G BG Lawn Rebecca B RB Sallis Hannah M HM Taylor Gemma M J GMJ Hemani Gibran G Jones Hannah J HJ Zammit Stanley S Davey Smith George G Munafò Marcus R MR

Psychological medicine 20191106 14

<h4>Background</h4>Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).<h4>Methods</h4>We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortiu ...[more]

PMID: 31689377

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Project description: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.

Project description:OBJECTIVES:To investigate whether the association between subjective wellbeing (subjective happiness and life satisfaction) and cardiometabolic health is causal. DESIGN:Two sample, bidirectional mendelian randomisation study. SETTING:Genetic data taken from various cohorts comprised of the general population (mostly individuals of European ancestry, plus a small proportion of other ancestries); follow-up analysis included individuals from the United Kingdom. PARTICIPANTS:Summary data were used from previous genome wide association studies (number of participants ranging from 83?198 to 339?224), which investigated traits related to cardiovascular or metabolic health, had the largest sample sizes, and consisted of the most similar populations while minimising sample overlap. A follow-up analysis included 337?112 individuals from the UK Biobank (54% female (n=181?363), mean age 56.87 years (standard deviation 8.00) at recruitment). MAIN OUTCOME MEASURES:Subjective wellbeing and 11 measures of cardiometabolic health (coronary artery disease; myocardial infarction; total, high density lipoprotein, and low density lipoprotein cholesterol; diastolic and systolic blood pressure; body fat; waist to hip ratio; waist circumference; and body mass index). RESULTS:Evidence of a causal effect of body mass index on subjective wellbeing was seen; each 1 kg/m2 increase in body mass index caused a -0.045 (95% confidence interval -0.084 to -0.006, P=0.02) standard deviation reduction in subjective wellbeing. Follow-up analysis of this association in an independent sample from the UK Biobank provided strong evidence of an effect of body mass index on satisfaction with health (?=-0.035 unit decrease in health satisfaction (95% confidence interval -0.043 to -0.027) per standard deviation increase in body mass index, P<0.001). No clear evidence of a causal effect was seen between subjective wellbeing and the other cardiometabolic health measures, in either direction. CONCLUSIONS:These results suggest that a higher body mass index is associated with a lower subjective wellbeing. A follow-up analysis confirmed this finding, suggesting that the effect in middle aged people could be driven by satisfaction with health. Body mass index is a modifiable determinant, and therefore, this study provides further motivation to tackle the obesity epidemic because of the knock-on effects of higher body mass index on subjective wellbeing.

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Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study.

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Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study.

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