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The effect of smoking intensity on all-cause and cause-specific mortality-a Mendelian randomization analysis.

Vie, Gunnhild Åberge; Wootton, Robyn E; Bjørngaard, Johan Håkon; Åsvold, Bjørn Olav; Taylor, AE; Gabrielsen, Maiken Elvestad; Davey, George Smith; Romundstad, Pål Richard; Munafo, Marcus R
Peer reviewed, Journal article
Published version
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Vie (Locked)
URI
https://hdl.handle.net/11250/2779064
Date
2019
Metadata
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Original version
International Journal of Epidemiology. 2019, 48 (5), 1438-1446.   10.1093/ije/dyz081
Abstract
Background

Smoking is an important cause of mortality and recent studies have suggested that even low-intensity smoking might be associated with increased mortality. Still, smoking is associated with lower socio-economic status as well as other potential risk factors, and disease onset might motivate smoking cessation, thus residual confounding and reverse causality might bias results. We aimed to assess the evidence of a causal relationship between smoking intensity and cause-specific as well as all-cause-mortality using Mendelian randomization analyses.

Methods

We included 56 019 participants from the Norwegian HUNT2 Study and 337 103 participants from UK Biobank, linked to national registry data on causes of death. We estimated associations of self-reported smoking as well as the genetic variant rs1051730 as an instrument for smoking intensity with all-cause and cause-specific mortality. We subsequently meta-analysed the results from the two cohorts.

Results

Each effect allele of the rs1051730 was associated with a 9% increased hazard of all-cause mortality [95% confidence interval (CI) 6–11] among ever smokers. Effect alleles were also associated with death by neoplasms [hazard ratio (HR) 1.11, 95% CI 1.06–1.15], circulatory diseases (HR 1.06, 95% CI 1.01–1.11) and respiratory diseases (HR 1.15, 95% CI 1.05–1.26) among ever smokers. The association was stronger among ever than never smokers for all-cause mortality (p < 0.001), neoplasms (p = 0.001) and respiratory diseases (p = 0.038).

Conclusions

Our results indicate a causal effect of smoking intensity on all-cause mortality and death by neoplasms and respiratory diseases. There was weaker evidence of a causal effect of smoking intensity on death by circulatory diseases.
Publisher
Oxford University Press
Journal
International Journal of Epidemiology

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