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.
| Original language | English |
|---|---|
| Pages (from-to) | 88-94 |
| Number of pages | 7 |
| Journal | British Journal of Psychiatry |
| Volume | 218 |
| Issue number | 2 |
| Early online date | 17 Sept 2019 |
| DOIs | |
| Publication status | Published - 28 Feb 2021 |
Data Availability Statement
For smoking initiation, we used summary data from the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN) GWAS as an exposure and outcome variable.Reference Liu, Jiang, Wedow, Li, Brazel and Chen10 GSCAN summary data about smoking heaviness and cessation from the GSCAN GWAS were used as an outcome variable only.Reference Liu, Jiang, Wedow, Li, Brazel and Chen10 For lifetime smoking, we used summary data from the GWAS in the UK Biobank for the exposure and outcome variables.Reference Wootton, Richmond, Stuijfzand, Lawn, Sallis and Taylor12For bipolar disorder, genome-wide significant SNPs (P < 5 × 10−8) from the most recently available GWAS were used as genetic instrument for the exposure.Reference Stahl, Breen, Forstner, McQuillin, Ripke and Trubetskoy15 When bipolar disorder was the outcome, we used the publicly available GWAS summary data made available by Psychiatric Genomics Consortium (https://www.med.unc.edu/pgc/results-and-downloads/).
Funding
R.E.W. is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the Medical Research Council (MC_UU_00011/7). This study was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the Department of Health.
Keywords
- bipolar affective disorders
- environmental
- Mendelian randomisation
- risk factor
- Smoking
ASJC Scopus subject areas
- Psychiatry and Mental health
