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. Bjorngaard; Claudia Flexeder; Satu Mannisto; Rebecca Hardy; Diana Kuh; Sarah J. Barry; Line Tang Mollehave; Charlotte Cerqueira; Nele Friedrich; Tobias N. Bonten; Raymond Noordam; Dennis O. Mook-Kanamori; Christian Taube; Leon E. Jessen; Alex McConnachie; Naveed Sattar; Mark Upton; Charles McSharry; Klaus Bonnelykke; Hans Bisgaard; Holger Schulz; Konstantin Strauch; Thomas Meitinger; Annette Peters; Harald Grallert; Ellen A. Nohr; Mika Kivimaki; Meena Kumari; Uwe Volker; Matthias Nauck; Henry Volzke; Chris Power; Elena Hypponen; Torben Hansen; Torben Jorgensen; Oluf Pedersen; Veikko Salomaa; Niels Grarup; Arnulf Langhammer; Pal R. Romundstad; Frank Skorpen; Jaakko Kaprio; Marcus R. Munafo; 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. Bjorngaard, Claudia Flexeder, Satu Mannisto, Rebecca Hardy, Diana Kuh, Sarah J. Barry, Line Tang Mollehave, Charlotte Cerqueira, Nele Friedrich, Tobias N. BontenRaymond Noordam, Dennis O. Mook-Kanamori, Christian Taube, Leon E. Jessen, Alex McConnachie, Naveed Sattar, Mark Upton, Charles McSharry, Klaus Bonnelykke, Hans Bisgaard, Holger Schulz, Konstantin Strauch, Thomas Meitinger, Annette Peters, Harald Grallert, Ellen A. Nohr, Mika Kivimaki, Meena Kumari, Uwe Volker, Matthias Nauck, Henry Volzke, Chris Power, Elena Hypponen, Torben Hansen, Torben Jorgensen, Oluf Pedersen, Veikko Salomaa, Niels Grarup, Arnulf Langhammer, Pal R. Romundstad, Frank Skorpen, Jaakko Kaprio, Marcus R. Munafo, 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.

Original language	English
Article number	2224
Number of pages	9
Journal	Scientific Reports
Volume	7
DOIs	https://doi.org/10.1038/s41598-017-01977-w
Publication status	Published - 22 May 2017

Keywords

hay fever
asthma
smoking

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Skaaby-etal-SR-2017-Investigating-the-casual-effect-of-smoking-on-hay-fever-and-asthmaFinal published version, 1.22 MBLicence: CC BY 4.0

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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., Bjorngaard, J. H., Flexeder, C., Mannisto, S., Hardy, R., Kuh, D., Barry, S. J., Mollehave, L. T., 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, [2224]. https://doi.org/10.1038/s41598-017-01977-w

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

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.",

keywords = "hay fever, asthma, smoking",

author = "Tea Skaaby and Taylor, {Amy E.} and Jacobsen, {Rikke K.} and Lavinia Paternoster and Thuesen, {Betina H.} and Ahluwalia, {Tarunveer S.} and Larsen, {Sofus C.} and Ang Zhou and Andrew Wong and Gabrielsen, {Maiken E.} and Bjorngaard, {Johan H.} and Claudia Flexeder and Satu Mannisto and Rebecca Hardy and Diana Kuh and Barry, {Sarah J.} and Mollehave, {Line Tang} and Charlotte Cerqueira and Nele Friedrich and Bonten, {Tobias N.} and Raymond Noordam and Mook-Kanamori, {Dennis O.} and Christian Taube and Jessen, {Leon E.} and Alex McConnachie and Naveed Sattar and Mark Upton and Charles McSharry and Klaus Bonnelykke and Hans Bisgaard and Holger Schulz and Konstantin Strauch and Thomas Meitinger and Annette Peters and Harald Grallert and Nohr, {Ellen A.} and Mika Kivimaki and Meena Kumari and Uwe Volker and Matthias Nauck and Henry Volzke and Chris Power and Elena Hypponen and Torben Hansen and Torben Jorgensen and Oluf Pedersen and Veikko Salomaa and Niels Grarup and Arnulf Langhammer and Romundstad, {Pal R.} and Frank Skorpen and Jaakko Kaprio and Munafo, {Marcus R.} and Allan Linneberg",

year = "2017",

month = may,

day = "22",

doi = "10.1038/s41598-017-01977-w",

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

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Skaaby, T, Taylor, AE, Jacobsen, RK, Paternoster, L, Thuesen, BH, Ahluwalia, TS, Larsen, SC, Zhou, A, Wong, A, Gabrielsen, ME, Bjorngaard, JH, Flexeder, C, Mannisto, S, Hardy, R, Kuh, D, Barry, SJ, Mollehave, LT, Cerqueira, C, Friedrich, N, Bonten, TN, Noordam, R, Mook-Kanamori, DO, Taube, C, Jessen, LE, McConnachie, A, Sattar, N, Upton, M, McSharry, C, Bonnelykke, K, Bisgaard, H, Schulz, H, Strauch, K, Meitinger, T, Peters, A, Grallert, H, Nohr, EA, Kivimaki, M, Kumari, M, Volker, U, Nauck, M, Volzke, H, Power, C, Hypponen, E, Hansen, T, Jorgensen, T, Pedersen, O, Salomaa, V, Grarup, N, Langhammer, A, Romundstad, PR, Skorpen, F, Kaprio, J, Munafo, MR & 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, vol. 7, 2224. https://doi.org/10.1038/s41598-017-01977-w

TY - JOUR

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 - Bjorngaard, Johan H.

AU - Flexeder, Claudia

AU - Mannisto, Satu

AU - Hardy, Rebecca

AU - Kuh, Diana

AU - Barry, Sarah J.

AU - Mollehave, Line Tang

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

AU - McSharry, Charles

AU - Bonnelykke, 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 - Volker, Uwe

AU - Nauck, Matthias

AU - Volzke, Henry

AU - Power, Chris

AU - Hypponen, Elena

AU - Hansen, Torben

AU - Jorgensen, Torben

AU - Pedersen, Oluf

AU - Salomaa, Veikko

AU - Grarup, Niels

AU - Langhammer, Arnulf

AU - Romundstad, Pal R.

AU - Skorpen, Frank

AU - Kaprio, Jaakko

AU - Munafo, Marcus R.

AU - Linneberg, Allan

PY - 2017/5/22

Y1 - 2017/5/22

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 - hay fever

KW - asthma

KW - smoking

U2 - 10.1038/s41598-017-01977-w

DO - 10.1038/s41598-017-01977-w

M3 - Article

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

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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