Genetic overlap and causal associations between smoking behaviours and mental health

Barkhuizen, Wikus; Dudbridge, Frank; Ronald, Angelica

doi:10.1038/s41598-021-93962-7

Cited by 22 publications

(23 citation statements)

References 98 publications

(103 reference statements)

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“…One retrospective study reported that 90% of patients with SCZ started smoking before the onset of their disease (Kelly & McCreadie, 1999), and longitudinal studies have pointed out that cigarette smoking increases the risk of developing SCZ and consistently reported a dose-response relationship of smoking quantity (Kendler et al, 2015;McGrath et al, 2016;Mustonen et al, 2018;Weiser et al, 2004). A previous MR study with 632,802 Caucasian population of smoking initiation GWAS also supported our finding, which indicated a causal role of smoking initiation in many psychiatric disorders, including SCZ, depression, and bipolar disorder (Barkhuizen et al, 2021).…”

Section: Discussionsupporting

confidence: 90%

“…Consistent and strong evidence has been reported for the causal effect of smoking initiation on SCZ among European-origin individuals (Barkhuizen et al, 2021; Gage et al, 2017; Wootton et al, 2020; Yuan et al, 2020); however, this issue has been less discussed in the Asian populations. Only one MR analysis in Asian participants with limited statistical power reported no significant causal association between smoking and SCZ (Chen et al, 2021).…”

Section: Discussionmentioning

confidence: 72%

“…The Mendelian randomization (MR) is a novel study design for investigating causality using a genetic approach. Reports suggest that smoking plays a causal role in SCZ (Barkhuizen et al, 2021; Gage et al, 2017; Wootton et al, 2020; Yuan et al, 2020). Further, the causal effect of SCZ on smoking initiation behaviors was also detected (Wootton et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Causal Relationship Between Smoking and Schizophrenia in Asia

Lai

Chen

et al. 2022

Preprint

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Cigarette smoking has been suggested to be associated with the risk of schizophrenia (SCZ) in observational studies. A significant causal effect of smoking on SCZ has been reported in the European population using the Mendelian randomization (MR) approach; however, no evidence of causality was found in participants from East Asia (EAS). Using the Taiwan Biobank (TWBB, sample size up to 79,989), we conducted genome-wide association studies (GWAS) to identify susceptibility loci for smoking behavior, which included the initiation of smoking and the onset age. To maximize the power of genetic discovery in the EAS population, we meta-analyzed GWAS from the TWBB and Biobank Japan (BBJ, sample size up to 165,436) for smoking traits. The GWAS for SCZ was taken from the Asia Psychiatric Genomics Consortium, which included 22,778 cases and 35,362 controls. We performed a two-sample MR to estimate the causality of smoking behavior on SCZ in the EAS population. In TWBB, we identified one novel locus that met genome-wide significance for onset age. In a meta-analysis of TWBB and BBJ, we identified two novel loci for smoking initiation. In MR, a marginal significance was found for the causality of smoking initiation on SCZ (odds ratio (OR) = 4.00, 95% confidence interval (CI) = 0.89-18.01, P = 0.071). Later onset age for smoking was causally associated with a lower risk of SCZ (OR for a per-year increase in onset = 0.96, 95% CI = 0.91-1.01) with a marginal significance (P = 0.098).

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Causal Relationship Between Smoking and Schizophrenia in Asia

Lai

Chen

et al. 2022

Preprint

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“…Different non-mutually exclusive mechanisms have been proposed to explain the link between tobacco smoking and mental health symptoms, including biological explanations such as nicotine-induced elevated dopamine release ( 6 , 43 ) and shared genetic vulnerability ( 44 ). On the behavioral level, both maladaptive coping and misattribution are thought to play a key role in the relationship between smoking and symptoms.…”

Section: Discussionmentioning

confidence: 99%

Differential trajectories of tobacco smoking in people at ultra-high risk for psychosis: Associations with clinical outcomes

Schirmbeck

Ven²,

Boyette³

et al. 2022

Front. Psychiatry

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ObjectivePeople at ultra-high risk (UHR) for psychosis have a high prevalence of tobacco smoking, and rates are even higher among the subgroup that later develop a psychotic disorder. However, the longitudinal relationship between the course of tobacco smoking and clinical outcomes in UHR subjects is unknown.MethodsWe investigated associations between tobacco smoking and clinical outcomes in a prospective study of UHR individuals (n = 324). Latent class mixed model analyses were used to identify trajectories of smoking severity. Mixed effects models were applied to investigate associations between smoking trajectory class and the course of attenuated psychotic symptoms (APS) and affective symptoms, as assessed using the CAARMS.ResultsWe identified four different classes of smoking trajectory: (i) Persistently High (n = 110), (ii) Decreasing (n = 29), (iii) Persistently Low (n = 165) and (iv) Increasing (n = 20). At two-year follow-up, there had been a greater increase in APS in the Persistently High class than for both the Persistently Low (ES = 9.77, SE = 4.87, p = 0.046) and Decreasing (ES = 18.18, SE = 7.61, p = 0.018) classes. There were no differences between smoking classes in the incidence of psychosis. There was a greater reduction in the severity of emotional disturbance and general symptoms in the Decreasing class than in the High (ES = −10.40, SE = 3.41, p = 0.003; ES = −22.36, SE = 10.07, p = 0.027), Increasing (ES = −11.35, SE = 4.55, p = 0.014; ES = −25.58, SE = 13.17, p = 0.050) and Low (ES = −11.38, SE = 3.29, p = 0.001; ES = −27.55, SE = 9.78, p = 0.005) classes, respectively.ConclusionsThese findings suggests that in UHR subjects persistent tobacco smoking is associated with an unfavorable course of psychotic symptoms, whereas decrease in the number of cigarettes smoked is associated with improvement in affective symptoms. Future research into smoking cessation interventions in the early stages of psychoses is required to shine light on the potential of modifying smoking behavior and its relation to clinical outcomes.

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“…Mendelian randomization approach is not biased by reverse causation or confounding when assuming that genetic instruments are directly associated with the exposure, genetic instruments are not related to confounders, and no pleiotropy is allowed from genetic instruments to outcome. Previous Mendelian randomization studies have suggested that smoking shows causal effect on schizophrenia, and vice versa 13 – 16 . However, most studies were conducted in Caucasian populations with a sufficient sample size for GWASs for smoking and schizophrenia.…”

Section: Introductionmentioning

confidence: 98%

Evaluation of the causal relationship between smoking and schizophrenia in East Asia

Lai

Chen

et al. 2022

Schizophr

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Cigarette smoking has been suggested to be associated with the risk of schizophrenia in observational studies. A significant causal effect of smoking on schizophrenia has been reported in European populations using the Mendelian randomization approach; however, no evidence of causality was found in participants from East Asia. Using Taiwan Biobank (TWBB), we conducted genome-wide association studies (GWAS) to identify susceptibility loci for smoking behaviors, including smoking initiation (N = 79,989) and the onset age (N = 15,582). We then meta-analyzed GWAS from TWBB and Biobank Japan (BBJ) with the total sample size of 245,425 for smoking initiation and 46,000 for onset age of smoking. The GWAS for schizophrenia was taken from the East Asia Psychiatric Genomics Consortium, which included 22,778 cases and 35,362 controls. We performed a two-sample Mendelian randomization to estimate the causality of smoking behaviors on schizophrenia in East Asia. In TWBB, we identified one locus that met genome-wide significance for onset age. In a meta-analysis of TWBB and BBJ, we identified two loci for smoking initiation. In Mendelian randomization, genetically predicted smoking initiation (odds ratio (OR) = 4.00, 95% confidence interval (CI) = 0.89–18.01, P = 0.071) and onset age (OR for a per-year increase = 0.96, 95% CI = 0.91–1.01, P = 0.098) were not significantly associated with schizophrenia; the direction of effect was consistent with European Ancestry samples, which had higher statistical power. These findings provide tentative evidence consistent with a causal role of smoking on the development of schizophrenia in East Asian populations.

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Genetic overlap and causal associations between smoking behaviours and mental health

Cited by 22 publications

References 98 publications

Evaluation of the Causal Relationship Between Smoking and Schizophrenia in Asia

Evaluation of the Causal Relationship Between Smoking and Schizophrenia in Asia

Differential trajectories of tobacco smoking in people at ultra-high risk for psychosis: Associations with clinical outcomes

Evaluation of the causal relationship between smoking and schizophrenia in East Asia

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