Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study
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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 OR IVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10 −8 , lifetime smoking OR IVW = 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 beta IVW = 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.
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There was no unambiguous evidence that having bipolar disorder causally influenced the risk of smoking-related outcome parameters.
“Vice versa, there was no unambiguous evidence that having BD causally influenced the risk of smoking-related outcome parameters (39).”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [39]
A bidirectional Mendelian randomization study found that smoking was an underlying risk factor for bipolar disorder (OR = 1.46 for smoking initiation, 95% CI 1.28-1.66, p < 0.001; OR = 1.72 for lifetime smoking, 95% CI 1.29-2.28, p < 0.001).
“Analyzing the results evidence emerged that smoking was an underlying risk factor for BD (OR = 1.46 for smoking initiation, 95% CI: 1.28–1.66, p < 0.001, and OR = 1.72 for lifetime smoking, 95% CI: 1.29–2.28, p < 0.001).”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [39]
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- Authors
- Vermeulen, J. M., Wootton, R. E., Treur, J. L., Sallis, H. M., Jones, H. J., Zammit, S., van den Brink, W., Goodwin, G. M., de Haan, L., & Munafò, M. R.
- Affiliations
- Amsterdam University Medical Centers (NL)
- University Hospitals Bristol NHS Foundation Trust (GB)
- University of Bristol (GB)
- Oxford Health NHS Foundation Trust (GB)
- Corresponding author
- Vermeulen, Jentien M.
- ORCID
- Venue
- The British Journal of Psychiatry
- Publisher
- Royal College of Psychiatrists
- Published
- 2019-09-17
- Volume
- 218
- Issue
- 2
- Pages
- 88-94
- ISSN
- 0007-1250 (ISSN-L)
- 1472-1465
- OpenAlex
- W2974729007
- Cited by
- 78
- References
- 62
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 13 · 2023: 11 · 2022: 14 · 2021: 11 · 2020: 13 · 2019: 3
- FWCI
- 8.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The British Journal of Psychiatry (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion, other-oa)
- Funders
- University Hospitals Bristol NHS Foundation Trust
- National Institute for Health and Care Research
- University of Bristol (MC_UU_00011/7)
- Medical Research Council (MC_UU_00011/7, MR/K023195/1, MR/L010305/1, MC_UU_00011)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- smoking, bipolar disorder, smoking initiation, lifetime smoking, smoking heaviness, smoking cessation, causal risk factors, bidirectional causality, severe mental illness, smoking prevention
- MeSH terms
- Bipolar Disorder, Humans, Smoking, Smoking Cessation, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Mendelian Randomization Analysis
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