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

BACKGROUND: Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS). METHODS: We co...

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Autores principales: Wootton, Robyn E., Richmond, Rebecca C., Stuijfzand, Bobby G., Lawn, Rebecca B., Sallis, Hannah M., Taylor, Gemma M. J., Hemani, Gibran, Jones, Hannah J., Zammit, Stanley, Davey Smith, George, Munafò, Marcus R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cambridge University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610182/
https://www.ncbi.nlm.nih.gov/pubmed/31689377
http://dx.doi.org/10.1017/S0033291719002678
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author Wootton, Robyn E.
Richmond, Rebecca C.
Stuijfzand, Bobby G.
Lawn, Rebecca B.
Sallis, Hannah M.
Taylor, Gemma M. J.
Hemani, Gibran
Jones, Hannah J.
Zammit, Stanley
Davey Smith, George
Munafò, Marcus R.
author_facet Wootton, Robyn E.
Richmond, Rebecca C.
Stuijfzand, Bobby G.
Lawn, Rebecca B.
Sallis, Hannah M.
Taylor, Gemma M. J.
Hemani, Gibran
Jones, Hannah J.
Zammit, Stanley
Davey Smith, George
Munafò, Marcus R.
author_sort Wootton, Robyn E.
collection PubMed
description BACKGROUND: Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS). METHODS: We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium. RESULTS: There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation. CONCLUSIONS: 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 on mental health.
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spelling pubmed-76101822020-11-13 Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study Wootton, Robyn E. Richmond, Rebecca C. Stuijfzand, Bobby G. Lawn, Rebecca B. Sallis, Hannah M. Taylor, Gemma M. J. Hemani, Gibran Jones, Hannah J. Zammit, Stanley Davey Smith, George Munafò, Marcus R. Psychol Med Original Articles BACKGROUND: Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS). METHODS: We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium. RESULTS: There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation. CONCLUSIONS: 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 on mental health. Cambridge University Press 2020-10 2019-11-06 /pmc/articles/PMC7610182/ /pubmed/31689377 http://dx.doi.org/10.1017/S0033291719002678 Text en © The Author(s) 2019 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Wootton, Robyn E.
Richmond, Rebecca C.
Stuijfzand, Bobby G.
Lawn, Rebecca B.
Sallis, Hannah M.
Taylor, Gemma M. J.
Hemani, Gibran
Jones, Hannah J.
Zammit, Stanley
Davey Smith, George
Munafò, Marcus R.
Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study
title Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study
title_full Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study
title_fullStr Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study
title_full_unstemmed Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study
title_short Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study
title_sort evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a mendelian randomisation study
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610182/
https://www.ncbi.nlm.nih.gov/pubmed/31689377
http://dx.doi.org/10.1017/S0033291719002678
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