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

Abstract

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. We aimed to investigate the direction and causal nature of the relationship between smoking and bipolar disorder we conducted a bidirectional Mendelian randomization (MR) study. 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 multiple analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger or Egger SIMEX, weighted median, weighted mode, and Steiger filtered analyses.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=1.44x10 -8 , lifetime smoking OR IVW =1.72, 95% CI=1.29-2.28, P=1.8x10 -4 ). The MR analyses of the liability of 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=2.9x10 -2 ). 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.3 Introduction.

As enigmáticas facetas genéticas, inflamatórias e ambientais e do transtorno bipolar: uma revisão integrativa

“…Além disso, o tabaco induz inflamação e estresse oxidativo, além de reduzir a capacidade de ligação da acetilcolina endógena nos receptores nicotínicos, sendo que a dificuldade de retirada da droga é uma evidência dessa alteração. Entretanto, as evidências são fracas para esse tema e mais estudos são necessários, mas levando em conta que o tabagismo é um hábito modificável, investimentos para prevenção e tratamento do tabagismo em pacientes com TB no mínimo contribuem para redução de danos e comorbidades (Vermeulen et al, 2021).…”