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Smoking and tobacco
Research
Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium
  1. Amy E Taylor1,2,
  2. Meg E Fluharty1,2,
  3. Johan H Bjørngaard3,4,
  4. Maiken Elvestad Gabrielsen5,
  5. Frank Skorpen5,
  6. Riccardo E Marioni6,7,8,
  7. Archie Campbell7,
  8. Jorgen Engmann9,
  9. Saira Saeed Mirza10,
  10. Anu Loukola11,
  11. Tiina Laatikainen12,13,14,
  12. Timo Partonen15,
  13. Marika Kaakinen16,17,
  14. Francesca Ducci18,
  15. Alana Cavadino19,
  16. Lise Lotte N Husemoen20,
  17. Tarunveer Singh Ahluwalia21,22,23,
  18. Rikke Kart Jacobsen20,
  19. Tea Skaaby20,
  20. Jeanette Frost Ebstrup20,
  21. Erik Lykke Mortensen24,
  22. Camelia C Minica25,
  23. Jacqueline M Vink25,
  24. Gonneke Willemsen25,
  25. Pedro Marques-Vidal26,
  26. Caroline E Dale27,
  27. Antoinette Amuzu27,
  28. Lucy T Lennon28,
  29. Jari Lahti29,30,
  30. Aarno Palotie31,32,33,
  31. Katri Räikkönen30,
  32. Andrew Wong34,
  33. Lavinia Paternoster1,35,
  34. Angelita Pui-Yee Wong36,37,
  35. L John Horwood38,
  36. Michael Murphy39,
  37. Elaine C Johnstone40,
  38. Martin A Kennedy41,
  39. Zdenka Pausova42,43,
  40. Tomáš Paus37,44,
  41. Yoav Ben-Shlomo35,
  42. Ellen A Nohr45,
  43. Diana Kuh34,
  44. Mika Kivimaki9,
  45. Johan G Eriksson30,46,47,48,49,50,
  46. Richard W Morris28,
  47. Juan P Casas27,51,
  48. Martin Preisig52,
  49. Dorret I Boomsma25,
  50. Allan Linneberg20,53,54,
  51. Chris Power19,
  52. Elina Hyppönen19,55,56,
  53. Juha Veijola57,
  54. Marjo-Riitta Jarvelin16,17,58,59,60,
  55. Tellervo Korhonen11,12,15,
  56. Henning Tiemeier61,
  57. Meena Kumari9,
  58. David J Porteous6,7,
  59. Caroline Hayward62,
  60. Pål R Romundstad3,
  61. George Davey Smith1,35,
  62. Marcus R Munafò1,2
  1. 1MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, UK
  2. 2UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK
  3. 3Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
  4. 4Forensic Department, Research Centre Bröset St. Olav's University Hospital Trondheim, Trondheim, Norway
  5. 5Faculty of Medicine, Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway
  6. 6Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
  7. 7Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  8. 8Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia
  9. 9Department of Epidemiology and Public Health, University College London, London, UK
  10. 10Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
  11. 11University of Helsinki, Hjelt institute, Helsinki, Finland
  12. 12University of Eastern Finland, Institute of Public Health & Clinical Nutrition, Kuopio, Finland
  13. 13Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
  14. 14Hospital District of North Karelia, Joensuu, Finland
  15. 15Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
  16. 16Institute of Health Sciences, FI-90014 University of Oulu, Finland
  17. 17Biocenter Oulu, FI-90014 University of Oulu, Finland
  18. 18South West London and St George's Mental Health Trust, London, UK
  19. 19Population, Policy and Practice, UCL Institute of Child Health, University College London, UK
  20. 20Research Centre for Prevention and Health, the Capital Region of Denmark, Denmark
  21. 21Metabolic Genetics Section, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
  22. 22Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  23. 23Danish Pediatric Asthma Center, Gentofte Hospital, The Capital Region, Copenhagen, Denmark.
  24. 24Institute of Public Health and Center for Healthy Aging, University of Copenhagen, Denmark
  25. 25Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands
  26. 26Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland
  27. 27Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK
  28. 28Department of Primary Care & Population Health, UCL, London, UK
  29. 29Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland
  30. 30Folkhälsan Research Centre, Helsinki, Finland
  31. 31Wellcome Trust Sanger Institute, Cambridge, UK
  32. 32The Medical and Population Genomics Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
  33. 33Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland
  34. 34MRC Unit for Lifelong Health, Ageing at UCL, UK
  35. 35School of Social and Community Medicine, University of Bristol, Bristol, UK
  36. 36Department of Psychology, University of Toronto, Toronto, Canada
  37. 37Rotman Research Institute, Toronto, Canada
  38. 38Department of Psychological Medicine, University of Otago, Christchurch, New Zealand
  39. 39Childhood Cancer Research Group, University of Oxford, Oxford, UK
  40. 40Department of Oncology, University of Oxford, Oxford, UK
  41. 41Department of Pathology, University of Otago, Christchurch, New Zealand
  42. 42Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada
  43. 43Hospital for Sick Children, Toronto, Canada
  44. 44Departments of Psychology and Psychiatry, University of Toronto, Toronto, Canada
  45. 45Institute for Clinical Research, University of Southern Denmark, Odense, Denmark
  46. 46Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland
  47. 47National Institute for Health and Welfare, Finland
  48. 48Department of General Practice and Primary health Care, University of Helsinki, Finland
  49. 49Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland
  50. 50Vasa Central Hospital, Vasa, Finland
  51. 51Institute of Cardiovascular Science, University College London, UK
  52. 52Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland
  53. 53Department of Clinical Experimental Research, Glostrup University Hospital, Denmark
  54. 54Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Denmark
  55. 55School of Population Health and Sansom Institute, University of South Australia, Adelaide, Australia
  56. 56South Australian Health and Medical Research Institute, Adelaide, Australia
  57. 57Department of Psychiatry, Oulu University Hospital, Oulu, Finland
  58. 58Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, UK
  59. 59Unit of Primary Care, Oulu University Hospital, Oulu, Finland
  60. 60Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland
  61. 61Department of Epidemiology and Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands
  62. 62Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  1. Correspondence to Dr Amy Taylor; amy.taylor{at}bristol.ac.uk

Abstract

Objectives To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach.

Design Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress.

Participants Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA).

Primary outcome measures Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis.

Results The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers.

Conclusions Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.

  • Mendelian randomisation
  • Smoking
  • Depression
  • Anxiety

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/bmjopen-2014-006141

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