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BMJ Open. 2014 Oct 7;4(10):e006141. doi: 10.1136/bmjopen-2014-006141.

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium.

Author information

  • 1MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, UK UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK.
  • 2Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway Forensic Department, Research Centre Bröset St. Olav's University Hospital Trondheim, Trondheim, Norway.
  • 3Faculty of Medicine, Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • 4Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
  • 5Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • 6Department of Epidemiology and Public Health, University College London, London, UK.
  • 7Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
  • 8University of Helsinki, Hjelt institute, Helsinki, Finland.
  • 9University of Eastern Finland, Institute of Public Health & Clinical Nutrition, Kuopio, Finland Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland Hospital District of North Karelia, Joensuu, Finland.
  • 10Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
  • 11Institute of Health Sciences, FI-90014 University of Oulu, Finland Biocenter Oulu, FI-90014 University of Oulu, Finland.
  • 12South West London and St George's Mental Health Trust, London, UK.
  • 13Population, Policy and Practice, UCL Institute of Child Health, University College London, UK.
  • 14Research Centre for Prevention and Health, the Capital Region of Denmark, Denmark.
  • 15Metabolic Genetics Section, Faculty of Health and Medical Sciences, Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Danish Pediatric Asthma Center, Gentofte Hospital, The Capital Region, Copenhagen, Denmark.
  • 16Institute of Public Health and Center for Healthy Aging, University of Copenhagen, Denmark.
  • 17Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands.
  • 18Department of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland.
  • 19Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
  • 20Department of Primary Care & Population Health, UCL, London, UK.
  • 21Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland Folkhälsan Research Centre, Helsinki, Finland.
  • 22Wellcome Trust Sanger Institute, Cambridge, UK The Medical and Population Genomics Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
  • 23Folkhälsan Research Centre, Helsinki, Finland.
  • 24MRC Unit for Lifelong Health, Ageing at UCL, UK.
  • 25MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, UK School of Social and Community Medicine, University of Bristol, Bristol, UK.
  • 26Department of Psychology, University of Toronto, Toronto, Canada Rotman Research Institute, Toronto, Canada.
  • 27Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
  • 28Childhood Cancer Research Group, University of Oxford, Oxford, UK.
  • 29Department of Oncology, University of Oxford, Oxford, UK.
  • 30Department of Pathology, University of Otago, Christchurch, New Zealand.
  • 31Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada Hospital for Sick Children, Toronto, Canada.
  • 32Rotman Research Institute, Toronto, Canada Departments of Psychology and Psychiatry, University of Toronto, Toronto, Canada.
  • 33School of Social and Community Medicine, University of Bristol, Bristol, UK.
  • 34Institute for Clinical Research, University of Southern Denmark, Odense, Denmark.
  • 35Folkhälsan Research Centre, Helsinki, Finland Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland National Institute for Health and Welfare, Finland Department of General Practice and Primary health Care, University of Helsinki, Finland Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland Vasa Central Hospital, Vasa, Finland.
  • 36Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK Institute of Cardiovascular Science, University College London, UK.
  • 37Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.
  • 38Research Centre for Prevention and Health, the Capital Region of Denmark, Denmark Department of Clinical Experimental Research, Glostrup University Hospital, Denmark Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Denmark.
  • 39Population, Policy and Practice, UCL Institute of Child Health, University College London, UK School of Population Health and Sansom Institute, University of South Australia, Adelaide, Australia South Australian Health and Medical Research Institute, Adelaide, Australia.
  • 40Department of Psychiatry, Oulu University Hospital, Oulu, Finland.
  • 41Institute of Health Sciences, FI-90014 University of Oulu, Finland Biocenter Oulu, FI-90014 University of Oulu, Finland Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, UK Unit of Primary Care, Oulu University Hospital, Oulu, Finland Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland.
  • 42University of Helsinki, Hjelt institute, Helsinki, Finland University of Eastern Finland, Institute of Public Health & Clinical Nutrition, Kuopio, Finland Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.
  • 43Department of Epidemiology and Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
  • 44Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • 45Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • 46Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

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.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

KEYWORDS:

Anxiety; Depression; Mendelian randomisation; Smoking

PMID:
25293386
[PubMed - indexed for MEDLINE]
PMCID:
PMC4187451
Free PMC Article

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