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 ORCID: https://orcid.org/0000-0002-2647-9211, van den Brink, Wim, Goodwin, Guy M., de Haan, Lieuwe and Munafò, Marcus R. 2021. Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study. British Journal of Psychiatry 218 (2) , pp. 88-94. 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:	Publication
Status:	Published
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:	06 Nov 2023 16:34
URI:	https://orca.cardiff.ac.uk/id/eprint/126049

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