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Causal effects of lifetime smoking on risk for depression and schizophrenia: Evidence from a Mendelian randomisation study

By Robyn E Wootton, Rebecca C Richmond, Bobby G Stuijfzand, Rebecca B Lawn, Hannah M Sallis, Gemma M J Taylor, Gibran Hemani, Hannah J Jones, Stanley Zammit, George Davey Smith, Marcus R. Munafò

Posted 01 Aug 2018
bioRxiv DOI: 10.1101/381301 (published DOI: 10.1017/S0033291719002678)

Smoking prevalence is higher amongst individuals with schizophrenia and depression compared to the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS). We conducted a GWAS of lifetime smoking behaviour (capturing smoking duration, heaviness and cessation) in a sample of 462,690 individuals from the UK Biobank, and validated the findings via two-sample MR analyses of positive control outcomes (e.g., lung cancer). Having established the validity of our instrument, we used bi-directional two-sample Mendelian randomisation to explore its effects on schizophrenia and depression. There was strong evidence to suggest smoking is a causal risk factor for both schizophrenia (OR = 2.27, 95% CI = 1.67 - 3.08, P < 0.001) and depression (OR = 1.99, 95% CI = 1.71 - 2.32, P < 0.001). We also found some evidence that genetic risk for both schizophrenia and depression cause increased lifetime smoking (β = 0.022, 95% CI = 0.005 - 0.038, P = 0.009; β= 0.091, 95% CI = 0.027 - 0.155, P = 0.005). These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking for mental health.

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