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

Vermeulen, Jentien M., Wootton, Robyn E., Treur, Jorien L., Sallis, Hannah M., Jones, Hannah J., Zammit, Stanley, van den Brink, Wim, Goodwin, Guy M., de Haan, Lieuwe and Munafò, Marcus R. 2019. Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study. British Journal of Psychiatry 10.1192/bjp.2019.202
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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 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.

Item Type: Article
Date Type: Published Online
Status: In Press
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Cambridge University Press (CUP)
ISSN: 0007-1250
Date of First Compliant Deposit: 15 October 2019
Date of Acceptance: 14 August 2019
Last Modified: 17 Oct 2019 17:32
URI: http://orca.cf.ac.uk/id/eprint/126049

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