Exploring causality of the association between smoking and Parkinson's disease

Valentina Gallo; Paolo Vineis; Mariagrazia Cancellieri; Paolo Chiodini; Roger A. Barker; Carol Brayne; Neil Pearce; Roel Vermeulen; Salvatore Panico; Bas Bueno-de-Mesquita; Nicola Vanacore; Lars Forsgren; Silvia Ramat; Eva Ardanaz; Larraitz Arriola; Jesper Peterson; Oskar Hansson; Diana Gavrila; Carlotta Sacerdote; Sabina Sieri; Tilman Kühn; Verena A. Katzke; Yvonne T. van der Schouw; Andreas Kyrozis; Giovanna Masala; Amalia Mattiello; Robert Perneczky; Lefkos Middleton; Rodolfo Saracci; Elio Riboli

doi:10.1093/ije/dyy230

Exploring causality of the association between smoking and Parkinson's disease

Valentina Gallo, Paolo Vineis, Mariagrazia Cancellieri, Paolo Chiodini, Roger A. Barker, Carol Brayne, Neil Pearce, Roel Vermeulen, Salvatore Panico, Bas Bueno-de-Mesquita, Nicola Vanacore, Lars Forsgren, Silvia Ramat, Eva Ardanaz, Larraitz Arriola, Jesper Peterson, Oskar Hansson, Diana Gavrila, Carlotta Sacerdote, Sabina SieriTilman Kühn, Verena A. Katzke, Yvonne T. van der Schouw, Andreas Kyrozis, Giovanna Masala, Amalia Mattiello, Robert Perneczky, Lefkos Middleton, Rodolfo Saracci, Elio Riboli

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.

Original language	English
Pages (from-to)	912-925
Number of pages	14
Journal	International Journal of Epidemiology
Volume	48
Issue number	3
DOIs	https://doi.org/10.1093/ije/dyy230
Publication status	Published - 2019

Subject classification (UKÄ)

Public Health, Global Health, Social Medicine and Epidemiology

Free keywords

causal inference
cohort study
EPIC
NeuroEPIC4PD
Parkinson’s disease
passive smoking
smoking
smoking patterns

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/ije/dyy230

Cite this

Gallo, V., Vineis, P., Cancellieri, M., Chiodini, P., Barker, R. A., Brayne, C., Pearce, N., Vermeulen, R., Panico, S., Bueno-de-Mesquita, B., Vanacore, N., Forsgren, L., Ramat, S., Ardanaz, E., Arriola, L., Peterson, J., Hansson, O., Gavrila, D., Sacerdote, C., ... Riboli, E. (2019). Exploring causality of the association between smoking and Parkinson's disease. International Journal of Epidemiology, 48(3), 912-925. https://doi.org/10.1093/ije/dyy230

@article{5717d67fb9c74411a8c6dd333fa8d233,

title = "Exploring causality of the association between smoking and Parkinson's disease",

abstract = "BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.",

keywords = "causal inference, cohort study, EPIC, NeuroEPIC4PD, Parkinson{\textquoteright}s disease, passive smoking, smoking, smoking patterns",

author = "Valentina Gallo and Paolo Vineis and Mariagrazia Cancellieri and Paolo Chiodini and Barker, {Roger A.} and Carol Brayne and Neil Pearce and Roel Vermeulen and Salvatore Panico and Bas Bueno-de-Mesquita and Nicola Vanacore and Lars Forsgren and Silvia Ramat and Eva Ardanaz and Larraitz Arriola and Jesper Peterson and Oskar Hansson and Diana Gavrila and Carlotta Sacerdote and Sabina Sieri and Tilman K{\"u}hn and Katzke, {Verena A.} and {van der Schouw}, {Yvonne T.} and Andreas Kyrozis and Giovanna Masala and Amalia Mattiello and Robert Perneczky and Lefkos Middleton and Rodolfo Saracci and Elio Riboli",

year = "2019",

doi = "10.1093/ije/dyy230",

language = "English",

volume = "48",

pages = "912--925",

journal = "International Journal of Epidemiology",

issn = "1464-3685",

publisher = "Oxford University Press",

number = "3",

}

Gallo, V, Vineis, P, Cancellieri, M, Chiodini, P, Barker, RA, Brayne, C, Pearce, N, Vermeulen, R, Panico, S, Bueno-de-Mesquita, B, Vanacore, N, Forsgren, L, Ramat, S, Ardanaz, E, Arriola, L, Peterson, J , Hansson, O, Gavrila, D, Sacerdote, C, Sieri, S, Kühn, T, Katzke, VA, van der Schouw, YT, Kyrozis, A, Masala, G, Mattiello, A, Perneczky, R, Middleton, L, Saracci, R & Riboli, E 2019, 'Exploring causality of the association between smoking and Parkinson's disease', International Journal of Epidemiology, vol. 48, no. 3, pp. 912-925. https://doi.org/10.1093/ije/dyy230

TY - JOUR

T1 - Exploring causality of the association between smoking and Parkinson's disease

AU - Gallo, Valentina

AU - Vineis, Paolo

AU - Cancellieri, Mariagrazia

AU - Chiodini, Paolo

AU - Barker, Roger A.

AU - Brayne, Carol

AU - Pearce, Neil

AU - Vermeulen, Roel

AU - Panico, Salvatore

AU - Bueno-de-Mesquita, Bas

AU - Vanacore, Nicola

AU - Forsgren, Lars

AU - Ramat, Silvia

AU - Ardanaz, Eva

AU - Arriola, Larraitz

AU - Peterson, Jesper

AU - Hansson, Oskar

AU - Gavrila, Diana

AU - Sacerdote, Carlotta

AU - Sieri, Sabina

AU - Kühn, Tilman

AU - Katzke, Verena A.

AU - van der Schouw, Yvonne T.

AU - Kyrozis, Andreas

AU - Masala, Giovanna

AU - Mattiello, Amalia

AU - Perneczky, Robert

AU - Middleton, Lefkos

AU - Saracci, Rodolfo

AU - Riboli, Elio

PY - 2019

Y1 - 2019

N2 - BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.

AB - BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait. METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset. RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding. CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.

KW - causal inference

KW - cohort study

KW - EPIC

KW - NeuroEPIC4PD

KW - Parkinson’s disease

KW - passive smoking

KW - smoking

KW - smoking patterns

U2 - 10.1093/ije/dyy230

DO - 10.1093/ije/dyy230

M3 - Article

C2 - 30462234

AN - SCOPUS:85072058871

SN - 1464-3685

VL - 48

SP - 912

EP - 925

JO - International Journal of Epidemiology

JF - International Journal of Epidemiology

IS - 3

ER -

Exploring causality of the association between smoking and Parkinson's disease

Abstract

Subject classification (UKÄ)

Free keywords

UN SDGs

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