Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium
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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.
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No causal effects of smoking heaviness on depression or anxiety in the Carta Consortium.
“A study of the Carta Consortium applied the same genetic instrument for smoking heaviness and found no causal effects on depression or anxiety (N=127,632) 49 .”
From A meta-review of "lifestyle psychiatry": the role of exercise, smoking, diet and sleep in the prevention and treatment of mental disorders (2020) · cites this paper as [49]
The Abstract Conclusions and Conclusion report that the Mendelian randomisation analyses did not support a causal role for smoking heaviness in depression or anxiety. The Abstract Results give a total analytic sample of 127,632 and identify the genetic variant used. But 'found no causal effects' is more definitive than the paper's conclusion: it explicitly says a small effect cannot be ruled out. (LLM, conf=0.85)
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Self-citationOpie, R. S., Jacka, F. N., Marx, W., Rocks, T., Young, C., & O’Neil, A. (2021) · Nutrients · doi:10.3390/nu13113766 · Cited by 16 · see citing works
- Authors
- Taylor, A. E., Fluharty, M. E., Bjørngaard, J. H., Gabrielsen, M. E., Skorpen, F., Marioni, R. E., Campbell, A., Engmann, J., Mirza, S. S., Loukola, A., Laatikainen, T., Partonen, T., Kaakinen, M., Ducci, F., Cavadino, A., Husemoen, L. L. N., Ahluwalia, T. S., Jacobsen, R. K., Skaaby, T., Ebstrup, J. F., Mortensen, E. L., Minica, C. C., Vink, J. M., Willemsen, G., Marques-Vidal, P., Dale, C. E., Amuzu, A., Lennon, L. T., Lahti, J., Palotie, A., Räikkönen, K., Wong, A., Paternoster, L., Wong, A. P.-Y., Horwood, L. J., Murphy, M., Johnstone, E. C., Kennedy, M. A., Pausova, Z., Paus, T., Ben-Shlomo, Y., Nohr, E. A., Kuh, D., Kivimaki, M., Eriksson, J. G., Morris, R. W., Casas, J. P., Preisig, M., Boomsma, D. I., Linneberg, A., Power, C., Hyppönen, E., Veijola, J., Jarvelin, M.-R., Korhonen, T., Tiemeier, H., Kumari, M., Porteous, D. J., Hayward, C., Romundstad, P. R., Smith, G. D., & Munafò, M. R.
- Affiliations
- University of Bristol (GB)
- Department of Public Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Norwegian University of Science and Technology (NO)
- The University of Queensland (AU)
- Institute of Genetics and Cancer (GB)
- University College London (GB)
- Erasmus MC (NL)
- University of Helsinki (FI)
- University of Eastern Finland (FI)
- Finnish Institute for Health and Welfare (FI)
- University of Oulu (FI)
- South West London and St George's Mental Health NHS Trust (GB)
- Capital Region of Denmark (DK)
- University of Copenhagen (DK)
- Department of Biological Psychology, Netherlands Twin Register, VU University, Amsterdam, The Netherlands
- Vrije Universiteit Amsterdam (NL)
- Centre Hospitalier Universitaire Vaudois (CH)
- London School of Hygiene & Tropical Medicine (GB)
- Broad Institute (US)
- Folkhälsans Forskningscentrum (FI)
- University of Toronto (CA)
- University of Otago (NZ)
- University of Oxford (GB)
- Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada
- School of Social and Community Medicine, University of Bristol, Bristol, UK
- University of Southern Denmark (DK)
- MRC Unit for Lifelong Health and Ageing (GB)
- Department of Epidemiology and Public Health, University College London, London, UK
- University of South Australia (AU)
- Oulu University Hospital (FI)
- Institute of Health Sciences, FI-90014 University of Oulu, Finland
- MRC Integrative Epidemiology Unit (IEU) at the University of Bristol, UK
- Corresponding author
- Taylor, Amy E
- ORCID
- Taylor, Amy E
- Fluharty, Meg E
- Gabrielsen, Maiken Elvestad
- Skorpen, Frank
- Marioni, Riccardo E
- Campbell, Archie
- Engmann, Jorgen
- Mirza, Saira Saeed
- Loukola, Anu
- Laatikainen, Tiina
- Partonen, Timo
- Kaakinen, Marika
- Cavadino, Alana
- Husemoen, Lise Lotte N
- Ahluwalia, Tarunveer Singh
- Jacobsen, Rikke Kart
- Skaaby, Tea
- Ebstrup, Jeanette Frost
- Mortensen, Erik Lykke
- Vink, Jacqueline M
- Willemsen, Gonneke
- Marques-Vidal, Pedro
- Dale, Caroline E
- Lennon, Lucy T
- Lahti, Jari
- Palotie, Aarno
- Räikkönen, Katri
- Wong, Andrew
- Paternoster, Lavinia
- Wong, Angelita Pui-Yee
- Horwood, L John
- Murphy, Michael
- Johnstone, Elaine C
- Kennedy, Martin A
- Paus, Tomáš
- Nohr, Ellen A
- Kuh, Diana
- Eriksson, Johan G
- Morris, Richard W
- Casas, Juan P
- Preisig, Martin
- Boomsma, Dorret I
- Linneberg, Allan
- Power, Chris
- Hyppönen, Elina
- Veijola, Juha
- Korhonen, Tellervo
- Tiemeier, Henning
- Porteous, David J
- Hayward, Caroline
- Romundstad, Pål R
- Smith, George Davey
- Venue
- BMJ Open
- Publisher
- BMJ
- Published
- 2014-10
- Volume
- 4
- Issue
- 10
- Pages
- e006141
- ISSN
- 2044-6055 (ISSN-L)
- PMC
- PMC4187451
- OpenAlex
- W2098492915
- Cited by
- 187
- References
- 70
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 8 · 2023: 13 · 2022: 8 · 2021: 21 · 2020: 55 · 2019: 14 · 2018: 19 · 2017: 9 · 2016: 13 · 2015: 9 · 2014: 1
- FWCI
- 7.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMJ Open (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- VU Research Portal (publishedVersion, other-oa)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- IRIS (submittedVersion, cc-by)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Open Access at Essex (University of Essex) (submittedVersion, cc-by)
- UniSA Research Outputs Repository (University of South Australia) (submittedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- BIBSYS Brage (BIBSYS (Norway)) (submittedVersion, cc-by)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Radboud Repository (Radboud University) (submittedVersion)
- Explore Bristol Research (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- National Science Foundation
- John D. and Catherine T. MacArthur Foundation (HS06516)
- Juvenile Diabetes Research Foundation International (U01 DK062418)
- March of Dimes Foundation
- Eli Lilly and Company
- Pfizer (HS06516)
- GlaxoSmithKline
- Heart and Stroke Foundation of Canada
- Helsingin Yliopisto
- University of Otago
- Norges Teknisk-Naturvitenskapelige Universitet
- Finska Läkaresällskapet
- Wellcome Trust (139635, 068545/Z/02), EU-FP7-, 084762, G0000934, MC_UU_12013/1, 213506, 102215, G0600705, 092731, 068545, 201413, 129680, WT084762, 129494, G1002319, 277849, 086684, HEALTH-F4-2007-201413, 076113)
- United Kingdom Clinical Research Collaboration
- Scottish Government (CZD/16/6)
- Government of the United Kingdom
- Folkhälsanin Tutkimussäätiö (129269)
- Cancer Research UK
- National Institute for Health and Care Research (G0000934, MC_UU_12013/1, PG/07/131/24254, G0500539, 0090049, G0600705)
- British Heart Foundation (RG/08/013/25942, PG/09/022, RG/13/16/30528, HS06516, G0600705, G0000934, PG/09/022/26739, PG/13/66/30442, PG/07/131/24254, 092731)
- Scottish Funding Council (HR03006)
- University College London
- University of Oxford
- European Commission (213506, 277849, NFBC1966, EU-FP7, G0500539, 911-09-032, 201413, 480-04-004, Framework 5 award QLG1-CT-2000-01643, QLG1‐CT‐2000‐01643, 5R01MH63706:02, 400-05-717)
- Health and Safety Executive
- University of Bristol (MC_UU_12013/1, 092731, G0600705, MC_UU_12013, MC_UU_12019/1, MC_UU_12013/6)
- National Research Foundation (105993, 129494)
- Cure Kids
- Canterbury Medical Research Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (122661, 118308, 25942, 139635, 105993, 201413, 129494, 139468, 120315, G0500539, 136895)
- Danmarks Grundforskningsfond
- ZonMw (Addiction‐31160008, Middelgroot‐911‐09‐032, 985-10-002, 400‐05‐717, 56-464-14192, 904-61-193, 911‐09‐032, 904-61-090, 31160008, 480‐04‐004, 050-060-810)
- Erasmus Universiteit Rotterdam
- Vrije Universiteit Amsterdam
- Academy of Finland (129680, 141 054, 24300796, QLG1-CT-2000-01643, 136895, G0600705, 141042, 092731, 5R01MH63706:02, 129269, 129494, 1114194, NFBC1986, #213506, 104781, 120315, 129269, 1114194, 24300796, 120315, 263836, NFBC1966, project grants 104781, 120315, 129269, 1114194, 139635, 104781)
- Erasmus Medisch Centrum (050-060-810)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (400‐05‐717, 050.060.810, 904-61-193, 904-61-090, 311-60008, MagW/ZonMW grants 904-61-090, 56‐464‐14192, Addiction-31160008, Spinozapremie 56-464-14192, 911-09-032, Addiction-31160008 Middelgroot-911-09-032, 985-10002, Middelgroot-911-09-032, 14192, 480-04-004, 904-61-090, 985-10-002)
- Juho Vainion Säätiö
- Novo Nordisk
- Signe ja Ane Gyllenbergin Säätiö (NFBC1966)
- Emil Aaltosen Säätiö
- Samfundet Folkhälsan
- Augustinus Fonden
- Oulun Yliopisto (75617, 129269, NFBC1966)
- Egmont Fonden
- Lotto New Zealand
- H. Lundbeck A/S
- Koç Üniversitesi
- National Institutes of Health (G0000934, 092731, -0001, 6r01hl087679-03, UL1TR001425, 5rl1mh083268-05, 400-05-717)
- Agency for Healthcare Research and Quality (HS06516)
- Chief Scientist Office, Scottish Government Health and Social Care Directorate (HR03006, CZD/16/6)
- Canadian Institutes of Health Research (136895, 2007-2012)
- Medical Research Council ([MC_UU_12019/1, G0802736, G0800612, MR/K023195/1, MC_UU_12013, MR/J01351X/1, G0500539, MR/J012165/1, MCUU12013/1, MR/K026992/1, HS06516, G0000934, G1002319, G0600705, MC_PC_15018, 092731, MC_UU_12013/6, MR/K023233/1, EU FP7)
- Economic and Social Research Council (MC_UU_12019/1, RES 596-28-0001, ES/K005774/1, ES/G007489/1, ES/J019119/1)
- National Health and Medical Research Council (1114194, G0000934)
- Health Research Council of New Zealand
- Biocenter, University of Oulu
- Norwegian Institute of Public Health
- National Institute on Aging (R01 AG1764406 S1, AG 13196, R37AG013196, R01AG013196, R01AG017644)
- National Heart, Lung, and Blood Institute (5R01 HL087679-02, HS06516, 5R01HL087679, R01 HL087679, HL36310, NHLBI: HL36310, 1RL1MH083268-01, G0000934, R01HL036310)
- National Institute of Mental Health (MH-077874, HEALTH-F4-2007-201413, R01MH063706, R01MH077874, RL1-MH083268, 1RL1MH083268-01, 5R01 MH63706:02, 1RL1MH083268, 5R01MH63706)
- National Institute on Drug Abuse (R01DA024413, R01DA018673)
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases (400-05-717, DK062418, U01DK062418)
- National Institute of Child Health and Human Development
- National Center for Advancing Translational Sciences
- FP7 Ideas: European Research Council (284167)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- smoking, depression, anxiety, psychological distress, smoking heaviness, causal inference, rs16969968, rs1051730, former smokers, never smokers, genetic variants
- MeSH terms
- Adolescent, Adult, Aged, Anxiety, Anxiety Disorders, Depression, Depressive Disorder, Female, Humans, Male, Middle Aged, Nerve Tissue Proteins, Receptors, Nicotinic, Smoking, Stress, Psychological, Causality, Young Adult, Mendelian Randomization Analysis
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