Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium

Tea Skaaby; Amy E Taylor; Rikke K Jacobsen; Lavinia Paternoster; Betina H Thuesen; Tarunveer S Ahluwalia; Sofus C Larsen; Ang Zhou; Andrew Wong; Maiken E Gabrielsen; Johan H Bjørngaard; Claudia Flexeder; Satu Männistö; Rebecca Hardy; Diana Kuh; Sarah J Barry; Line Tang Møllehave; Charlotte Cerqueira; Nele Friedrich; Tobias N Bonten; Raymond Noordam; Dennis O Mook-Kanamori; Christian Taube; Leon E Jessen; Alex McConnachie; Naveed Sattar; Mark N Upton; Charles McSharry; Klaus Bønnelykke; Hans Bisgaard; Holger Schulz; Konstantin Strauch; Thomas Meitinger; Annette Peters; Harald Grallert; Ellen A Nohr; Mika Kivimaki; Meena Kumari; Uwe Völker; Matthias Nauck; Henry Völzke; Chris Power; Elina Hyppönen; Torben Hansen; Torben Jørgensen; Oluf Pedersen; Veikko Salomaa; Niels Grarup; Arnulf Langhammer; Pål R Romundstad; Frank Skorpen; Jaakko Kaprio; Marcus R Munafò; Allan Linneberg

doi:10.1038/s41598-017-01977-w

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium

Tea Skaaby, Amy E Taylor, Rikke K Jacobsen, Lavinia Paternoster, Betina H Thuesen, Tarunveer S Ahluwalia, Sofus C Larsen, Ang Zhou, Andrew Wong, Maiken E Gabrielsen, Johan H Bjørngaard, Claudia Flexeder, Satu Männistö, Rebecca Hardy, Diana Kuh, Sarah J Barry, Line Tang Møllehave, Charlotte Cerqueira, Nele Friedrich, Tobias N BontenRaymond Noordam, Dennis O Mook-Kanamori, Christian Taube, Leon E Jessen, Alex McConnachie, Naveed Sattar, Mark N Upton, Charles McSharry, Klaus Bønnelykke, Hans Bisgaard, Holger Schulz, Konstantin Strauch, Thomas Meitinger, Annette Peters, Harald Grallert, Ellen A Nohr, Mika Kivimaki, Meena Kumari, Uwe Völker, Matthias Nauck, Henry Völzke, Chris Power, Elina Hyppönen, Torben Hansen, Torben Jørgensen, Oluf Pedersen, Veikko Salomaa, Niels Grarup, Arnulf Langhammer, Pål R Romundstad, Frank Skorpen, Jaakko Kaprio, Marcus R Munafò, Allan Linneberg

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Abstract

Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

Originalsprog	Engelsk
Artikelnummer	2224
Tidsskrift	Scientific Reports
Vol/bind	7
Udgave nummer	1
Antal sider	9
ISSN	2045-2322
DOI	https://doi.org/10.1038/s41598-017-01977-w
Status	Udgivet - 1 dec. 2017

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10.1038/s41598-017-01977-wLicens: CC BY

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization metaanalysis in the CARTA consortiumForlagets udgivne version, 1,37 MBLicens: CC BY

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Skaaby, T., Taylor, A. E., Jacobsen, R. K., Paternoster, L., Thuesen, B. H., Ahluwalia, T. S., Larsen, S. C., Zhou, A., Wong, A., Gabrielsen, M. E., Bjørngaard, J. H., Flexeder, C., Männistö, S., Hardy, R., Kuh, D., Barry, S. J., Tang Møllehave, L., Cerqueira, C., Friedrich, N., ... Linneberg, A. (2017). Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium. Scientific Reports, 7(1), [2224]. https://doi.org/10.1038/s41598-017-01977-w

Skaaby, T, Taylor, AE, Jacobsen, RK, Paternoster, L, Thuesen, BH, Ahluwalia, TS, Larsen, SC, Zhou, A, Wong, A, Gabrielsen, ME, Bjørngaard, JH, Flexeder, C, Männistö, S, Hardy, R, Kuh, D, Barry, SJ, Tang Møllehave, L, Cerqueira, C, Friedrich, N, Bonten, TN, Noordam, R, Mook-Kanamori, DO, Taube, C, Jessen, LE, McConnachie, A, Sattar, N, Upton, MN, McSharry, C, Bønnelykke, K, Bisgaard, H, Schulz, H, Strauch, K, Meitinger, T, Peters, A, Grallert, H, Nohr, EA, Kivimaki, M, Kumari, M, Völker, U, Nauck, M, Völzke, H, Power, C, Hyppönen, E, Hansen, T, Jørgensen, T, Pedersen, O, Salomaa, V, Grarup, N, Langhammer, A, Romundstad, PR, Skorpen, F, Kaprio, J, R Munafò, M & Linneberg, A 2017, 'Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium', Scientific Reports, bind 7, nr. 1, 2224. https://doi.org/10.1038/s41598-017-01977-w

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abstract = "Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.",

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T1 - Investigating the causal effect of smoking on hay fever and asthma

T2 - a Mendelian randomization meta-analysis in the CARTA consortium

AU - Skaaby, Tea

AU - Taylor, Amy E

AU - Jacobsen, Rikke K

AU - Paternoster, Lavinia

AU - Thuesen, Betina H

AU - Ahluwalia, Tarunveer S

AU - Larsen, Sofus C

AU - Zhou, Ang

AU - Wong, Andrew

AU - Gabrielsen, Maiken E

AU - Bjørngaard, Johan H

AU - Flexeder, Claudia

AU - Männistö, Satu

AU - Hardy, Rebecca

AU - Kuh, Diana

AU - Barry, Sarah J

AU - Tang Møllehave, Line

AU - Cerqueira, Charlotte

AU - Friedrich, Nele

AU - Bonten, Tobias N

AU - Noordam, Raymond

AU - Mook-Kanamori, Dennis O

AU - Taube, Christian

AU - Jessen, Leon E

AU - McConnachie, Alex

AU - Sattar, Naveed

AU - Upton, Mark N

AU - McSharry, Charles

AU - Bønnelykke, Klaus

AU - Bisgaard, Hans

AU - Schulz, Holger

AU - Strauch, Konstantin

AU - Meitinger, Thomas

AU - Peters, Annette

AU - Grallert, Harald

AU - Nohr, Ellen A

AU - Kivimaki, Mika

AU - Kumari, Meena

AU - Völker, Uwe

AU - Nauck, Matthias

AU - Völzke, Henry

AU - Power, Chris

AU - Hyppönen, Elina

AU - Hansen, Torben

AU - Jørgensen, Torben

AU - Pedersen, Oluf

AU - Salomaa, Veikko

AU - Grarup, Niels

AU - Langhammer, Arnulf

AU - Romundstad, Pål R

AU - Skorpen, Frank

AU - Kaprio, Jaakko

AU - R Munafò, Marcus

AU - Linneberg, Allan

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

AB - Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76; P < 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86; P < 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998; P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02; P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11; P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.

KW - Journal Article

U2 - 10.1038/s41598-017-01977-w

DO - 10.1038/s41598-017-01977-w

M3 - Journal article

C2 - 28533558

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 2224

ER -

Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortium

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