Abstract | BACKGROUND: 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.
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Authors | Jentien M Vermeulen, Robyn E Wootton, Jorien L Treur, Hannah M Sallis, Hannah J Jones, Stanley Zammit, Wim van den Brink, Guy M Goodwin, Lieuwe de Haan, Marcus R Munafò |
Journal | The British journal of psychiatry : the journal of mental science
(Br J Psychiatry)
Vol. 218
Issue 2
Pg. 88-94
(02 2021)
ISSN: 1472-1465 [Electronic] England |
PMID | 31526406
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Topics |
- Bipolar Disorder
(etiology, genetics)
- Genome-Wide Association Study
- Humans
- Mendelian Randomization Analysis
- Polymorphism, Single Nucleotide
- Smoking
- Smoking Cessation
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