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Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study

Published online by Cambridge University Press:  17 September 2019

Jentien M. Vermeulen
Affiliation:
Medical Doctor, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, The Netherlands
Robyn E. Wootton
Affiliation:
Post-doc Researcher, School of Psychological Science, University of Bristol; MRC Integrative Epidemiology Unit, University of Bristol; and NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and the University of Bristol, UK
Jorien L. Treur
Affiliation:
Post-doc Researcher, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, The Netherlands
Hannah M. Sallis
Affiliation:
Post-doc Researcher, School of Psychological Science, University of Bristol; and MRC Integrative Epidemiology Unit, University of Bristol, UK
Hannah J. Jones
Affiliation:
Post-doc Researcher, Department of Population Health Sciences, Bristol Medical School, University of Bristol; and MRC Integrative Epidemiology Unit, University of Bristol, UK
Stanley Zammit
Affiliation:
Professor of Psychiatric Epidemiology, Department of Population Health Sciences, Bristol Medical School, University of Bristol, UK; and MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, University of Cardiff, UK
Wim van den Brink
Affiliation:
Emeritus Professor of Addiction, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, The Netherlands
Guy M. Goodwin
Affiliation:
Professor of Psychiatry, Department of Psychiatry, University of Oxford; and Oxford Health NHS Foundation Trust, Oxford, UK
Lieuwe de Haan
Affiliation:
Professor of Psychotic Disorders, Department of Psychiatry, Amsterdam UMC, University of Amsterdam, The Netherlands
Marcus R. Munafò
Affiliation:
Professor of Biological Psychology, School of Psychological Science, University of Bristol, Bristol; MRC Integrative Epidemiology Unit, University of Bristol; and UK Centre for Tobacco and Alcohol Studies, University of Bristol, UK
Corresponding

Abstract

Background

There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.

Aims

We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.

Method

We used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.

Results

Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).

Conclusions

These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.

Type
Papers
Copyright
Copyright © The Royal College of Psychiatrists 2019

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Footnotes

Declaration of interest W.v.d.B received fees in the past 3 years from Indivior, C&A Pharma, Opiant and Angelini. G.M.G. is a National Institute for Health Research (NIHR) Emeritus Senior Investigator, holds shares in P1vital and has served as consultant, advisor or CME speaker in the past 3 years for Allergan, Angelini, Compass Pathways, MSD, Lundbeck (/Otsuka and /Takeda), Medscape, Minervra, P1Vital, Pfizer, Sage, Servier, Shire and Sun Pharma.

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Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study
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