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

Amy E Taylor; Meg E Fluharty; Johan H Bjørngaard; Maiken Elvestad Gabrielsen; Frank Skorpen; Riccardo E Marioni; Archie Campbell; Jorgen Engmann; Saira Saeed Mirza; Anu Loukola; Tiina Laatikainen; Timo Partonen; Marika Kaakinen; Francesca Ducci; Alana Cavadino; Lise Lotte N Husemoen; Tarun Veer Singh Ahluwalia; Rikke Kart Jacobsen; Tea Skaaby; Jeanette Frost Ebstrup; Erik Lykke Mortensen; Camelia C Minica; Jacqueline M Vink; Gonneke Willemsen; Pedro Marques-Vidal; Caroline E Dale; Antoinette Amuzu; Lucy T Lennon; Jari Lahti; Aarno Palotie; Katri Räikkönen; Andrew Wong; Lavinia Paternoster; Angelita Pui-Yee Wong; L John Horwood; Michael Murphy; Elaine C Johnstone; Martin A Kennedy; Zdenka Pausova; Tomáš Paus; Yoav Ben-Shlomo; Ellen A Nohr; Diana Kuh; Mika Kivimaki; Johan G Eriksson; Richard W Morris; Juan P Casas; Martin Preisig; Dorret I Boomsma; Allan Linneberg; Chris Power; Elina Hyppönen; Juha Veijola; Marjo-Riitta Jarvelin; Tellervo Korhonen; Henning Tiemeier; Meena Kumari; David J Porteous; Caroline Hayward; Pål R Romundstad; George Davey Smith; Marcus R Munafò

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

Amy E Taylor, Meg E Fluharty, Johan H Bjørngaard, Maiken Elvestad Gabrielsen, Frank Skorpen, Riccardo E Marioni, Archie Campbell, Jorgen Engmann, Saira Saeed Mirza, Anu Loukola, Tiina Laatikainen, Timo Partonen, Marika Kaakinen, Francesca Ducci, Alana Cavadino, Lise Lotte N Husemoen, Tarun Veer Singh Ahluwalia, Rikke Kart Jacobsen, Tea Skaaby, Jeanette Frost EbstrupErik Lykke Mortensen, Camelia C Minica, Jacqueline M Vink, Gonneke Willemsen, Pedro Marques-Vidal, Caroline E Dale, Antoinette Amuzu, Lucy T Lennon, Jari Lahti, Aarno Palotie, Katri Räikkönen, Andrew Wong, Lavinia Paternoster, Angelita Pui-Yee Wong, L John Horwood, Michael Murphy, Elaine C Johnstone, Martin A Kennedy, Zdenka Pausova, Tomáš Paus, Yoav Ben-Shlomo, Ellen A Nohr, Diana Kuh, Mika Kivimaki, Johan G Eriksson, Richard W Morris, Juan P Casas, Martin Preisig, Dorret I Boomsma, Allan Linneberg, Chris Power, Elina Hyppönen, Juha Veijola, Marjo-Riitta Jarvelin, Tellervo Korhonen, Henning Tiemeier, Meena Kumari, David J Porteous, Caroline Hayward, Pål R Romundstad, George Davey Smith, Marcus R Munafò

74 Citations (Scopus)

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 language	English
Article number	e006141
Journal	B M J Open
Volume	4
Issue number	10
Pages (from-to)	1-13
Number of pages	13
ISSN	2044-6055
DOIs	https://doi.org/10.1136/bmjopen-2014-006141
Publication status	Published - 2014

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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. V. S., Jacobsen, R. K., Skaaby, T., ... Munafò, M. R. (2014). Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium. B M J Open, 4(10), 1-13. [e006141]. https://doi.org/10.1136/bmjopen-2014-006141

Taylor, AE, Fluharty, ME, Bjørngaard, JH, Gabrielsen, ME, Skorpen, F, Marioni, RE, Campbell, A, Engmann, J, Mirza, SS, Loukola, A, Laatikainen, T, Partonen, T, Kaakinen, M, Ducci, F, Cavadino, A, Husemoen, LLN, Ahluwalia, TVS, Jacobsen, RK, Skaaby, T, Ebstrup, JF, Mortensen, EL, 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, Wong, AP-Y, 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, Jarvelin, M-R, Korhonen, T, Tiemeier, H, Kumari, M, Porteous, DJ, Hayward, C, Romundstad, PR, Smith, GD & Munafò, MR 2014, 'Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium', B M J Open, vol. 4, no. 10, e006141, pp. 1-13. https://doi.org/10.1136/bmjopen-2014-006141

@article{c9697ef4c7aa43378123dc766f7d86bd,

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 = "Taylor, {Amy E} and Fluharty, {Meg E} and Bj{\o}rngaard, {Johan H} and Gabrielsen, {Maiken Elvestad} and Frank Skorpen and Marioni, {Riccardo E} and Archie Campbell and Jorgen Engmann and Mirza, {Saira Saeed} and Anu Loukola and Tiina Laatikainen and Timo Partonen and Marika Kaakinen and Francesca Ducci and Alana Cavadino and Husemoen, {Lise Lotte N} and Ahluwalia, {Tarun Veer Singh} and Jacobsen, {Rikke Kart} and Tea Skaaby and Ebstrup, {Jeanette Frost} and Mortensen, {Erik Lykke} and Minica, {Camelia C} and Vink, {Jacqueline M} and Gonneke Willemsen and Pedro Marques-Vidal and Dale, {Caroline E} and Antoinette Amuzu and Lennon, {Lucy T} and Jari Lahti and Aarno Palotie and Katri R{\"a}ikk{\"o}nen and Andrew Wong and Lavinia Paternoster and Wong, {Angelita Pui-Yee} and Horwood, {L John} and Michael Murphy and Johnstone, {Elaine C} and Kennedy, {Martin A} and Zdenka Pausova and Tom{\'a}{\v s} Paus and Yoav Ben-Shlomo and Nohr, {Ellen A} and Diana Kuh and Mika Kivimaki and Eriksson, {Johan G} and Morris, {Richard W} and Casas, {Juan P} and Martin Preisig and Boomsma, {Dorret I} and Allan Linneberg and Chris Power and Elina Hypp{\"o}nen and Juha Veijola and Marjo-Riitta Jarvelin and Tellervo Korhonen and Henning Tiemeier and Meena Kumari and Porteous, {David J} and Caroline Hayward and Romundstad, {P{\aa}l R} and Smith, {George Davey} and Munaf{\`o}, {Marcus R}",

note = "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.",

year = "2014",

doi = "10.1136/bmjopen-2014-006141",

language = "English",

volume = "4",

pages = "1--13",

journal = "BMJ Open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

number = "10",

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TY - JOUR

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

T2 - the CARTA consortium

AU - Taylor, Amy E

AU - Fluharty, Meg E

AU - Bjørngaard, Johan H

AU - Gabrielsen, Maiken Elvestad

AU - Skorpen, Frank

AU - Marioni, Riccardo E

AU - Campbell, Archie

AU - Engmann, Jorgen

AU - Mirza, Saira Saeed

AU - Loukola, Anu

AU - Laatikainen, Tiina

AU - Partonen, Timo

AU - Kaakinen, Marika

AU - Ducci, Francesca

AU - Cavadino, Alana

AU - Husemoen, Lise Lotte N

AU - Ahluwalia, Tarun Veer Singh

AU - Jacobsen, Rikke Kart

AU - Skaaby, Tea

AU - Ebstrup, Jeanette Frost

AU - Mortensen, Erik Lykke

AU - Minica, Camelia C

AU - Vink, Jacqueline M

AU - Willemsen, Gonneke

AU - Marques-Vidal, Pedro

AU - Dale, Caroline E

AU - Amuzu, Antoinette

AU - Lennon, Lucy T

AU - Lahti, Jari

AU - Palotie, Aarno

AU - Räikkönen, Katri

AU - Wong, Andrew

AU - Paternoster, Lavinia

AU - Wong, Angelita Pui-Yee

AU - Horwood, L John

AU - Murphy, Michael

AU - Johnstone, Elaine C

AU - Kennedy, Martin A

AU - Pausova, Zdenka

AU - Paus, Tomáš

AU - Ben-Shlomo, Yoav

AU - Nohr, Ellen A

AU - Kuh, Diana

AU - Kivimaki, Mika

AU - Eriksson, Johan G

AU - Morris, Richard W

AU - Casas, Juan P

AU - Preisig, Martin

AU - Boomsma, Dorret I

AU - Linneberg, Allan

AU - Power, Chris

AU - Hyppönen, Elina

AU - Veijola, Juha

AU - Jarvelin, Marjo-Riitta

AU - Korhonen, Tellervo

AU - Tiemeier, Henning

AU - Kumari, Meena

AU - Porteous, David J

AU - Hayward, Caroline

AU - Romundstad, Pål R

AU - Smith, George Davey

AU - Munafò, Marcus R

N1 - 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.

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 - Journal article

C2 - 25293386

SN - 2044-6055

VL - 4

SP - 1

EP - 13

JO - BMJ Open

JF - BMJ Open

IS - 10

M1 - e006141

ER -

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

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