scholarly journals Examining the effect of smoking on suicidal ideation and attempts: A triangulation of epidemiological approaches

2019 ◽  
Author(s):  
Ruth Harrison ◽  
Marcus R Munafò ◽  
George Davey Smith ◽  
Robyn E Wootton
Keyword(s):  
Suicidal Behaviour ◽  
Causal Effect ◽  
Smoking Status ◽  
Strong Association ◽  
Smoking Initiation ◽  
Smoking Behaviour ◽  
Mendelian Randomisation ◽  
Snp Analysis ◽  
Suicidal Thoughts ◽  
Smoking Behaviours

AbstractBackgroundPrevious literature has demonstrated a strong association between cigarette smoking and suicide-related behaviours, characterised as ideation, plans, attempts and suicide related death. This association has not previously been examined in a causal inference framework and has important implications for suicide prevention strategies.AimsWe aimed to examine the evidence for an association between smoking behaviours (initiation, smoking status, heaviness, lifetime smoking) and suicidal thoughts or attempts by triangulating across observational and Mendelian randomisation (MR) analyses.MethodsFirst, in the UK Biobank, we calculate observed associations between smoking behaviours and suicidal thoughts or attempts. Second, we used Mendelian randomisation (MR) to explore the relationship between smoking and suicide using genetic variants as instruments to reduce bias from residual confounding and reverse causation.ResultsOur observational analysis showed a relationship between smoking behaviour and suicidal behaviour, particularly between smoking initiation and suicidal attempts (OR = 2.07, 95% CI = 1.91 to 2.26, p<0.001). The MR analysis and single SNP analysis, however, did not support this. Despite past literature showing a positive dose-response relationship our results showed no clear evidence for a causal effect of smoking on suicidal behaviours.ConclusionThis was the first MR study to explore the effect of smoking on suicidal behaviours. Our results suggest that, despite observed associations, there is no strong evidence for a causal effect of smoking behaviour on suicidal behaviour. Our evidence suggests that further research is needed into alternative risk factors for suicide which might make better intervention targets.

scholarly journals Examining the effect of smoking on suicidal ideation and attempts: triangulation of epidemiological approaches

2020 ◽  
Vol 217 (6) ◽  
pp. 701-707 ◽  
Author(s):  
Ruth Harrison ◽  
Marcus R. Munafò ◽  
George Davey Smith ◽  
Robyn E. Wootton
Keyword(s):  
Suicidal Ideation ◽  
Odds Ratio ◽  
Suicide Attempts ◽  
Causal Effect ◽  
Smoking Status ◽  
Strong Association ◽  
Mendelian Randomisation ◽  
Polymorphism Analysis ◽  
Suicidal Thoughts ◽  
Smoking Behaviours

BackgroundPrevious literature has demonstrated a strong association between cigarette smoking, suicidal ideation and suicide attempts. This association has not previously been examined in a causal inference framework and could have important implications for suicide prevention strategies.AimsWe aimed to examine the evidence for an association between smoking behaviours (initiation, smoking status, heaviness, lifetime smoking) and suicidal thoughts or attempts by triangulating across observational and Mendelian randomisation analyses.MethodFirst, in the UK Biobank, we calculated observed associations between smoking behaviours and suicidal thoughts or attempts. Second, we used Mendelian randomisation to explore the relationship between smoking and suicide attempts and ideation, using genetic variants as instruments to reduce bias from residual confounding and reverse causation.ResultsOur observational analysis showed a relationship between smoking behaviour, suicidal ideation and attempts, particularly between smoking initiation and suicide attempts (odds ratio, 2.07; 95% CI 1.91–2.26; P < 0.001). The Mendelian randomisation analysis and single-nucleotide polymorphism analysis, however, did not support this (odds ratio for lifetime smoking on suicidal ideation, 0.050; 95% CI −0.027 to 0.127; odds ratio on suicide attempts, 0.053; 95% CI, −0.003 to 0.110). Despite past literature showing a positive dose-response relationship, our results showed no clear evidence for a causal effect of smoking on suicidal ideation or attempts.ConclusionsThis was the first Mendelian randomisation study to explore the effect of smoking on suicidal ideation and attempts. Our results suggest that, despite observed associations, there is no clear evidence for a causal effect.

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

2019 ◽  
Vol 50 (14) ◽  
pp. 2435-2443 ◽  
Author(s):  
Robyn E. Wootton ◽  
Rebecca C. Richmond ◽  
Bobby G. Stuijfzand ◽  
Rebecca B. Lawn ◽  
Hannah M. Sallis ◽  
...  
Keyword(s):  
Causal Effect ◽  
Association Studies ◽  
Smoking Initiation ◽  
Smoking Behaviour ◽  
Positive Control ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Weak Evidence ◽  
Smoking Duration ◽  
The Uk

AbstractBackgroundSmoking 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).MethodsWe 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.ResultsThere 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 (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.ConclusionsThese 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.

scholarly journals Smoking and COVID-19 outcomes: an observational and Mendelian randomisation study using the UK Biobank cohort

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217080
Author(s):  
Ashley K Clift ◽  
Adam von Ende ◽  
Pui San Tan ◽  
Hannah M Sallis ◽  
Nicola Lindson ◽  
...  
Keyword(s):  
Large Scale ◽  
Hospital Admissions ◽  
Causal Effect ◽  
Smoking Status ◽  
Smoking Initiation ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Never Smokers ◽  
The Uk ◽  
Analytical Approaches

BackgroundConflicting evidence has emerged regarding the relevance of smoking on risk of COVID-19 and its severity.MethodsWe undertook large-scale observational and Mendelian randomisation (MR) analyses using UK Biobank. Most recent smoking status was determined from primary care records (70.8%) and UK Biobank questionnaire data (29.2%). COVID-19 outcomes were derived from Public Health England SARS-CoV-2 testing data, hospital admissions data, and death certificates (until 18 August 2020). Logistic regression was used to estimate associations between smoking status and confirmed SARS-CoV-2 infection, COVID-19-related hospitalisation, and COVID-19-related death. Inverse variance-weighted MR analyses using established genetic instruments for smoking initiation and smoking heaviness were undertaken (reported per SD increase).ResultsThere were 421 469 eligible participants, 1649 confirmed infections, 968 COVID-19-related hospitalisations and 444 COVID-19-related deaths. Compared with never-smokers, current smokers had higher risks of hospitalisation (OR 1.80, 95% CI 1.26 to 2.29) and mortality (smoking 1–9/day: OR 2.14, 95% CI 0.87 to 5.24; 10–19/day: OR 5.91, 95% CI 3.66 to 9.54; 20+/day: OR 6.11, 95% CI 3.59 to 10.42). In MR analyses of 281 105 White British participants, genetically predicted propensity to initiate smoking was associated with higher risks of infection (OR 1.45, 95% CI 1.10 to 1.91) and hospitalisation (OR 1.60, 95% CI 1.13 to 2.27). Genetically predicted higher number of cigarettes smoked per day was associated with higher risks of all outcomes (infection OR 2.51, 95% CI 1.20 to 5.24; hospitalisation OR 5.08, 95% CI 2.04 to 12.66; and death OR 10.02, 95% CI 2.53 to 39.72).InterpretationCongruent results from two analytical approaches support a causal effect of smoking on risk of severe COVID-19.

scholarly journals The effect of body mass index on smoking behaviour and nicotine metabolism: a Mendelian randomization study

2018 ◽  
Author(s):  
Amy E. Taylor ◽  
Rebecca C. Richmond ◽  
Teemu Palviainen ◽  
Anu Loukola ◽  
Jaakko Kaprio ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Smoking Initiation ◽  
Smoking Behaviour ◽  
Bidirectional Association ◽  
Metabolite Ratio ◽  
Nicotine Metabolite Ratio

AbstractBackgroundGiven clear evidence that smoking lowers weight, it is possible that individuals with higher body mass index (BMI) smoke in order to lose or maintain their weight.Methods and FindingsWe undertook Mendelian randomization analyses using 97 genetic variants associated with BMI. We performed two sample Mendelian randomization analyses of the effects of BMI on smoking behaviour in UK Biobank (N=335,921) and the Tobacco and Genetics consortium genomewide association study (GWAS) (N≤74,035) respectively, and two sample Mendelian randomization analyses of the effects of BMI on cotinine levels (N≤4,548) and nicotine metabolite ratio (N≤1,518) in published GWAS, and smoking-related DNA methylation in the Avon Longitudinal Study of Parents and Children (N≤846).In inverse variance weighted Mendelian randomization analysis, there was evidence that higher BMI was causally associated with smoking initiation (OR for ever vs never smoking per one SD increase in BMI: 1.19, 95% CI: 1.11 to 1.27) and smoking heaviness (1.45 additional cigarettes smoked per day per SD increase in BMI, 95% CI: 1.03 to 1.86), but little evidence for a causal effect with smoking cessation. Results were broadly similar using pleiotropy robust methods (MR-Egger, median and weighted mode regression). These results were supported by evidence for a causal effect of BMI on DNA methylation at the aryl-hydrocarbon receptor repressor (AHRR) locus. There was no strong evidence that BMI was causally associated with cotinine, but suggestive evidence for a causal negative association with the nicotine metabolite ratio.ConclusionsThere is a causal bidirectional association between BMI and smoking, but the relationship is likely to be complex due to opposing effects on behaviour and metabolism. It may be useful to consider BMI and smoking together when designing prevention strategies to minimise the effects of these risk factors on health outcomes.

scholarly journals A multivariable Mendelian randomization analysis investigating smoking and alcohol consumption in oral and oropharyngeal cancer

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark Gormley ◽  
Tom Dudding ◽  
Eleanor Sanderson ◽  
Richard M. Martin ◽  
Steven Thomas ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Alcohol Consumption ◽  
Oropharyngeal Cancer ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Strong Association ◽  
Smoking Behaviour ◽  
Standard Deviation Increase ◽  
Independent Effects

AbstractThe independent effects of smoking and alcohol in head and neck cancer are not clear, given the strong association between these risk factors. Their apparent synergistic effect reported in previous observational studies may also underestimate independent effects. Here we report multivariable Mendelian randomization performed in a two-sample approach using summary data on 6,034 oral/oropharyngeal cases and 6,585 controls from a recent genome-wide association study. Our results demonstrate strong evidence for an independent causal effect of smoking on oral/oropharyngeal cancer (IVW OR 2.6, 95% CI = 1.7, 3.9 per standard deviation increase in lifetime smoking behaviour) and an independent causal effect of alcohol consumption when controlling for smoking (IVW OR 2.1, 95% CI = 1.1, 3.8 per standard deviation increase in drinks consumed per week). This suggests the possibility that the causal effect of alcohol may have been underestimated. However, the extent to which alcohol is modified by smoking requires further investigation.

scholarly journals Youth vaping and smoking and parental vaping: a cross-sectional survey

2020 ◽  
Author(s):  
Michael Green ◽  
Linsay Gray ◽  
Helen Sweeting
Keyword(s):  
Smoking Status ◽  
Smoking Initiation ◽  
Smoking Behaviour ◽  
Youth Smoking ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Unmeasured Confounding ◽  
Increase Risk ◽  
Alternative Scenarios ◽  
Negative Impacts

Abstract Background: Concerns remain about potential negative impacts of e-cigarettes including possibilities that: youth e-cigarette use (vaping) increases risk of youth smoking; and vaping by parents may have impacts on their children’s vaping and smoking behaviour. Methods: With cross-sectional data from 3291 youth aged 10-15 years from the Understanding Society Survey, we estimated effects of youth vaping on youth smoking (ever, current and initiation in the past year), and of parental vaping on youth smoking and vaping, and examined whether the latter differed by parental smoking status. Propensity weighting was used to adjust for measured confounders and estimate effects of vaping under alternative scenarios of no vaping vs universal adoption, and vs observed vaping levels. E-values were calculated to assess the strength of unmeasured confounding influences needed to negate our estimates. Results: Associations between youth vaping and youth smoking were attenuated considerably by adjustment for measured confounders. Estimated effects of youth vaping on youth smoking were stronger comparing no use to universal adoption (e.g. OR for smoking initiation: 32.5; 95% CI: 9.8-107.1) than to observed levels of youth vaping (OR: 4.4; 0.6-30.9). Relatively strong unmeasured confounding would be needed to explain these effects. Associations between parental vaping and youth vaping were explained by measured confounders. However, estimates for parental vaping on youth smoking indicated effects, especially for youth with ex-smoking parents (e.g. OR for smoking initiation: 11.3; 2.7-46.4) rather than youth with currently smoking parents (OR: 1.0; 0.2-6.4). Relatively weak unmeasured confounding could explain these parental vaping effects. Conclusions: While results for youth vaping and youth smoking associations indicated support for underlying propensities, estimated effects still required considerable unmeasured confounding to be explained fully. However, these estimates from cross-sectional data could also be explained by smoking leading to vaping. Stronger estimates for universal vaping adoption vs observed usage, indicated that if youth vaping does increase risk of youth smoking, this effect may be stronger in the general population of youth, than among those youth who typically vape. Associations of parental vaping with youth smoking and vaping were either explained by measured confounding or could be relatively easily explained by unmeasured confounding.

scholarly journals Estimation of causal effects of a time-varying exposure at multiple time points through Multivariable Mendelian randomization

2022 ◽  
Author(s):  
Eleanor Sanderson ◽  
Tom G Richardson ◽  
Tim T Morris ◽  
Kate Tilling ◽  
George Davey Smith
Keyword(s):  
Direct Effect ◽  
Genetic Variants ◽  
Causal Effect ◽  
Smoking Behaviour ◽  
Causal Effects ◽  
Mendelian Randomisation ◽  
Multiple Time ◽  
Time Points ◽  
Time Periods ◽  
Multiple Time Points

Mendelian Randomisation (MR) is a powerful tool in epidemiology to estimate the causal effect of an exposure on an outcome in the presence of unobserved confounding, by utilising genetic variants as instrumental variables (IVs) for the exposure. The effects obtained from MR studies are often interpreted as the lifetime effect of the exposure in question. However, the causal effects of many exposures are thought to vary throughout an individual's lifetime and there may be periods during which an exposure has more of an effect on a particular outcome. Multivariable MR (MVMR) is an extension of MR that allows for multiple, potentially highly related, exposures to be included in an MR estimation. MVMR estimates the direct effect of each exposure on the outcome conditional on all of the other exposures included in the estimation. We explore the use of MVMR to estimate the direct effect of a single exposure at different time points in an individual's lifetime on an outcome. We use simulations to illustrate the interpretation of the results from such analyses and the key assumptions required. We show that causal effects at different time periods can be estimated through MVMR when the association between the genetic variants used as instruments and the exposure measured at those time periods varies, however this estimation will not necessarily identify exact time periods over which an exposure has the most effect on the outcome. We illustrate the method through estimation of the causal effects of childhood and adult BMI on smoking behaviour.

scholarly journals The effect of smoking on multiple sclerosis: a mendelian randomization study

2020 ◽  
Author(s):  
Ruth E Mitchell ◽  
Kirsty Bates ◽  
Robyn E Wootton ◽  
Adil Harroud ◽  
J. Brent Richards ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Association Studies ◽  
Meta Analysis ◽  
Smoking Initiation ◽  
Smoking Behaviour ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Smoking Duration

AbstractThe causes of multiple sclerosis (MS) remain unknown. Smoking has been associated with MS in observational studies and is often thought of as an environmental risk factor. We used two-sample Mendelian Randomization (MR) to examined whether this association is causal using genetic variants identified in genome-wide association studies (GWAS) as associated with smoking. We assessed both smoking initiation and lifetime smoking behaviour (which captures smoking duration, heaviness and cessation). There was very limited evidence for a meaningful effect of smoking on MS susceptibility was measured using summary statistics from the International Multiple Sclerosis Genetics Consortium (IMSGC) meta-analysis, including 14,802 cases and 26,703 controls. There was no clear evidence for an effect of smoking on the risk of developing MS (smoking initiation: odds ratio [OR] 1.03, 95% confidence interval [CI] 0.92-1.61; lifetime smoking: OR 1.10, 95% CI 0.87-1.40). These findings suggest that smoking does not have a detrimental consequence on MS susceptibility. Further work is needed to determine the causal effect of smoking on MS progression.

Cigarette smoking and schizophrenia: Mendelian randomisation study

2020 ◽  
pp. 1-6
Author(s):  
Jianhua Chen ◽  
Ruirui Chen ◽  
Siying Xiang ◽  
Ningning Li ◽  
Chengwen Gao ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Association Studies ◽  
Smoking Initiation ◽  
Sensitivity Analyses ◽  
Mendelian Randomisation ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Complex Behaviour ◽  
Asian Populations ◽  
Smoking Behaviours

Background The link between schizophrenia and cigarette smoking has been well established through observational studies. However, the cause–effect relationship remains unclear. Aims We conducted Mendelian randomisation analyses to assess any causal relationship between genetic variants related to four smoking-related traits and the risk of schizophrenia. Method We performed a two-sample Mendelian randomisation using summary statistics from genome-wide association studies (GWAS) of smoking-related traits and schizophrenia (7711 cases, 18 327 controls) in East Asian populations. Single nucleotide polymorphisms (SNPs) correlated with smoking behaviours (smoking initiation, smoking cessation, age at smoking initiation and quantity of smoking) were investigated in relation to schizophrenia using the inverse-variance weighted (IVW) method. Further sensitivity analyses, including Mendelian randomisation-Egger (MR-Egger), weighted median estimates and leave-one-out analysis, were used to test the consistency of the results. Results The associated SNPs for the four smoking behaviours were not significantly associated with schizophrenia status. Pleiotropy did not inappropriately affect the results. Conclusions Cigarette smoking is a complex behaviour in people with schizophrenia. Understanding factors underlying the observed association remains important; however, our findings do not support a causal role of smoking in influencing risk of schizophrenia.

scholarly journals Youth vaping and smoking and parental vaping: a panel survey

2020 ◽  
Author(s):  
Michael Green ◽  
Linsay Gray ◽  
Helen Sweeting
Keyword(s):  
Smoking Status ◽  
Smoking Initiation ◽  
Smoking Behaviour ◽  
Residual Effects ◽  
Cigarette Use ◽  
Youth Smoking ◽  
Unmeasured Confounding ◽  
Youth Population ◽  
Negative Impacts ◽  
The Uk

Abstract Background: Concerns remain about potential negative impacts of e-cigarettes including possibilities that: youth e-cigarette use (vaping) increases risk of youth smoking; and vaping by parents may have impacts on their children’s vaping and smoking behaviour.Methods: With panel data from 3291 youth aged 10-15 years from the 7th wave of the UK Understanding Society Survey (2015-2017), we estimated effects of youth vaping on youth smoking (ever, current and past year initiation), and of parental vaping on youth smoking and vaping, and examined whether the latter differed by parental smoking status. Propensity weighting was used to adjust for measured confounders and estimate average effects of vaping for all youth, and among youth who vaped. E-values were calculated to assess the strength of unmeasured confounding influences needed to negate our estimates.Results: Associations between youth vaping and youth smoking were attenuated considerably by adjustment for measured confounders. Estimated average effects of youth vaping on youth smoking were stronger for all youth (e.g. OR for smoking initiation: 32.5; 95% CI: 9.8-107.1) than among youth who vaped (OR: 4.4; 0.6-30.9). Relatively strong unmeasured confounding would be needed to explain these effects. Associations between parental vaping and youth vaping were explained by measured confounders. Estimates indicated effects of parental vaping on youth smoking, especially for youth with ex-smoking parents (e.g. OR for smoking initiation: 11.3; 2.7-46.4) rather than youth with currently smoking parents (OR: 1.0; 0.2-6.4), but these could be explained by relatively weak unmeasured confounding.Conclusions: While measured confounding accounted for much of the associations between youth vaping and youth smoking, indicating support for underlying propensities, our estimates suggested residual effects that could only be explained away by considerable unmeasured confounding or by smoking leading to vaping. Estimated effects of youth vaping on youth smoking were stronger among the general youth population than among the small group of youth who actually vaped. Associations of parental vaping with youth smoking and vaping were either explained by measured confounding or could be relatively easily explained by unmeasured confounding.

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