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

A.E. Taylor, M.E. Fluharty, J.H. Bjørngaard, M. Elvestad Gabrielsen, F. Skorpen, R.E. Marioni, A. Campbell, J. Engmann, S. Saeed Mirza, A. Loukola, T. Laatikainen, T. Partonen, M. Kaakinen, F. Ducci, A. Cavadino, L.L.N. Husemoen, T. Singh Ahluwalia, R. Kart Jacobsen, T. Skaaby, J. Frost Ebstrup & 42 others E. Lykke Mortensen, C.C. Minica, J.M. Vink, G. Willemsen, P. Marques-Vidal, C.E. Dale, A. Amuzu, L.T. Lennon, J. Lahti, A. Palotie, K. Räikkönen, A. Wong, L. Paternoster, A Pui-Yee Wong, L.J. Horwood, M. Murphy, E.C. Johnstone, M.A. Kennedy, Z. Pausova, T. Paus, Y. Ben-Shlomo, E.A. Nohr, D Kuh, M. Kivimaki, J.G. Eriksson, R.W. Morris, J.P. Casas, M. Preisig, D.I. Boomsma, A. Linneberg, C. Power, E. Hyppönen, J. Veijola, M.R. Järvelin, T. Korhonen, H. Tiemeier, M. Kumari, D.J. Porteous, C. Hayward, P.R. Romundstad, G.D. Smith, M.R. Munafo

Research output: Contribution to Journal › Article › Academic › peer-review

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.
Original languageEnglish
Article numbere006141
Number of pages13
JournalBMJ Open
Volume4
Issue number10
DOIs
Publication statusPublished - 2014

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Mendelian Randomization Analysis
Tobacco
Meta-Analysis
Anxiety
Smoking
Alcohols
Depression
Psychology
Research
Proxy
Random Allocation
Tobacco Products
Alleles

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Taylor, A. E., Fluharty, M. E., Bjørngaard, J. H., Elvestad Gabrielsen, M., Skorpen, F., Marioni, R. E., ... Munafo, M. R. (2014). Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium. BMJ Open, 4(10), [e006141]. https://doi.org/10.1136/bmjopen-2014-006141
Taylor, A.E. ; Fluharty, M.E. ; Bjørngaard, J.H. ; Elvestad Gabrielsen, M. ; Skorpen, F. ; Marioni, R.E. ; Campbell, A. ; Engmann, J. ; Saeed Mirza, S. ; Loukola, A. ; Laatikainen, T. ; Partonen, T. ; Kaakinen, M. ; Ducci, F. ; Cavadino, A. ; Husemoen, L.L.N. ; Singh Ahluwalia, T. ; Kart Jacobsen, R. ; Skaaby, T. ; Frost Ebstrup, J. ; Lykke Mortensen, E. ; 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. ; Pui-Yee Wong, A ; 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. ; Järvelin, M.R. ; Korhonen, T. ; Tiemeier, H. ; Kumari, M. ; Porteous, D.J. ; Hayward, C. ; Romundstad, P.R. ; Smith, G.D. ; Munafo, M.R. / Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium. In: BMJ Open. 2014 ; Vol. 4, No. 10.
@article{132679257a644595894e2f25a1e36d0f,
title = "Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium",
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.",
author = "A.E. Taylor and M.E. Fluharty and J.H. Bj{\o}rngaard and {Elvestad Gabrielsen}, M. and F. Skorpen and R.E. Marioni and A. Campbell and J. Engmann and {Saeed Mirza}, S. and A. Loukola and T. Laatikainen and T. Partonen and M. Kaakinen and F. Ducci and A. Cavadino and L.L.N. Husemoen and {Singh Ahluwalia}, T. and {Kart Jacobsen}, R. and T. Skaaby and {Frost Ebstrup}, J. and {Lykke Mortensen}, E. and C.C. Minica and J.M. Vink and G. Willemsen and P. Marques-Vidal and C.E. Dale and A. Amuzu and L.T. Lennon and J. Lahti and A. Palotie and K. R{\"a}ikk{\"o}nen and A. Wong and L. Paternoster and {Pui-Yee Wong}, A and L.J. Horwood and M. Murphy and E.C. Johnstone and M.A. Kennedy and Z. Pausova and T. Paus and Y. Ben-Shlomo and E.A. Nohr and D Kuh and M. Kivimaki and J.G. Eriksson and R.W. Morris and J.P. Casas and M. Preisig and D.I. Boomsma and A. Linneberg and C. Power and E. Hypp{\"o}nen and J. Veijola and M.R. J{\"a}rvelin and T. Korhonen and H. Tiemeier and M. Kumari and D.J. Porteous and C. Hayward and P.R. Romundstad and G.D. Smith and M.R. Munafo",
year = "2014",
doi = "10.1136/bmjopen-2014-006141",
language = "English",
volume = "4",
journal = "BMJ Open",
issn = "2044-6055",
publisher = "BMJ Publishing Group",
number = "10",

}

Taylor, AE, Fluharty, ME, Bjørngaard, JH, Elvestad Gabrielsen, M, Skorpen, F, Marioni, RE, Campbell, A, Engmann, J, Saeed Mirza, S, Loukola, A, Laatikainen, T, Partonen, T, Kaakinen, M, Ducci, F, Cavadino, A, Husemoen, LLN, Singh Ahluwalia, T, Kart Jacobsen, R, Skaaby, T, Frost Ebstrup, J, Lykke Mortensen, E, Minica, CC, Vink, JM, Willemsen, G, Marques-Vidal, P, Dale, CE, Amuzu, A, Lennon, LT, Lahti, J, Palotie, A, Räikkönen, K, Wong, A, Paternoster, L, Pui-Yee Wong, A, Horwood, LJ, Murphy, M, Johnstone, EC, Kennedy, MA, Pausova, Z, Paus, T, Ben-Shlomo, Y, Nohr, EA, Kuh, D, Kivimaki, M, Eriksson, JG, Morris, RW, Casas, JP, Preisig, M, Boomsma, DI, Linneberg, A, Power, C, Hyppönen, E, Veijola, J, Järvelin, MR, Korhonen, T, Tiemeier, H, Kumari, M, Porteous, DJ, Hayward, C, Romundstad, PR, Smith, GD & Munafo, MR 2014, 'Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium' BMJ Open, vol. 4, no. 10, e006141. https://doi.org/10.1136/bmjopen-2014-006141

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium. / Taylor, A.E.; Fluharty, M.E.; Bjørngaard, J.H.; Elvestad Gabrielsen, M.; Skorpen, F.; Marioni, R.E.; Campbell, A.; Engmann, J.; Saeed Mirza, S.; Loukola, A.; Laatikainen, T.; Partonen, T.; Kaakinen, M.; Ducci, F.; Cavadino, A.; Husemoen, L.L.N.; Singh Ahluwalia, T.; Kart Jacobsen, R.; Skaaby, T.; Frost Ebstrup, J.; Lykke Mortensen, E.; 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.; Pui-Yee Wong, A; 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.; Järvelin, M.R.; Korhonen, T.; Tiemeier, H.; Kumari, M.; Porteous, D.J.; Hayward, C.; Romundstad, P.R.; Smith, G.D.; Munafo, M.R.

In: BMJ Open, Vol. 4, No. 10, e006141, 2014.

Research output: Contribution to Journal › Article › Academic › peer-review

TY - JOUR

T1 - Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium

AU - Taylor, A.E.

AU - Fluharty, M.E.

AU - Bjørngaard, J.H.

AU - Elvestad Gabrielsen, M.

AU - Skorpen, F.

AU - Marioni, R.E.

AU - Campbell, A.

AU - Engmann, J.

AU - Saeed Mirza, S.

AU - Loukola, A.

AU - Laatikainen, T.

AU - Partonen, T.

AU - Kaakinen, M.

AU - Ducci, F.

AU - Cavadino, A.

AU - Husemoen, L.L.N.

AU - Singh Ahluwalia, T.

AU - Kart Jacobsen, R.

AU - Skaaby, T.

AU - Frost Ebstrup, J.

AU - Lykke Mortensen, E.

AU - Minica, C.C.

AU - Vink, J.M.

AU - Willemsen, G.

AU - Marques-Vidal, P.

AU - Dale, C.E.

AU - Amuzu, A.

AU - Lennon, L.T.

AU - Lahti, J.

AU - Palotie, A.

AU - Räikkönen, K.

AU - Wong, A.

AU - Paternoster, L.

AU - Pui-Yee Wong, A

AU - Horwood, L.J.

AU - Murphy, M.

AU - Johnstone, E.C.

AU - Kennedy, M.A.

AU - Pausova, Z.

AU - Paus, T.

AU - Ben-Shlomo, Y.

AU - Nohr, E.A.

AU - Kuh, D

AU - Kivimaki, M.

AU - Eriksson, J.G.

AU - Morris, R.W.

AU - Casas, J.P.

AU - Preisig, M.

AU - Boomsma, D.I.

AU - Linneberg, A.

AU - Power, C.

AU - Hyppönen, E.

AU - Veijola, J.

AU - Järvelin, M.R.

AU - Korhonen, T.

AU - Tiemeier, H.

AU - Kumari, M.

AU - Porteous, D.J.

AU - Hayward, C.

AU - Romundstad, P.R.

AU - Smith, G.D.

AU - Munafo, M.R.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

U2 - 10.1136/bmjopen-2014-006141

DO - 10.1136/bmjopen-2014-006141

M3 - Article

VL - 4

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 10

M1 - e006141

ER -

Taylor AE, Fluharty ME, Bjørngaard JH, Elvestad Gabrielsen M, Skorpen F, Marioni RE et al. Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium. BMJ Open. 2014;4(10). e006141. https://doi.org/10.1136/bmjopen-2014-006141

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