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

Tea Skaaby; Amy E. Taylor; Rikke K. Jacobsen; Lavinia Paternoster; Betina Heinsbæk 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 Eyrich Jessen; Alex McConnachie; Naveed Sattar; Mark N. Upton; Charles McSharry; Klaus Bonnelykke; Hans Flinker 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 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 consortiumn

Tea Skaaby, Amy E. Taylor, Rikke K. Jacobsen, Lavinia Paternoster, Betina Heinsbæk 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 Eyrich Jessen, Alex McConnachie, Naveed Sattar, Mark N. Upton, Charles McSharry, Klaus Bonnelykke, Hans Flinker 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 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
Journal	Scientific Reports
Volume	7
Issue number	1
Number of pages	9
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-017-01977-w
Publication status	Published - 2017
Externally published	Yes

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Skaaby, T., Taylor, A. E., Jacobsen, R. K., Paternoster, L., Thuesen, B. H., S. Ahluwalia, T., 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 consortiumn. Scientific Reports, 7(1), Article 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 consortiumn",

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.",

author = "Tea Skaaby and Taylor, {Amy E.} and Jacobsen, {Rikke K.} and Lavinia Paternoster and Thuesen, {Betina Heinsb{\ae}k} and {S. Ahluwalia}, Tarunveer 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 Eyrich} and Alex McConnachie and Naveed Sattar and Upton, {Mark N.} and Charles McSharry and Klaus Bonnelykke and Bisgaard, {Hans Flinker} 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 V{\"o}lker and Matthias Nauck and Henry V{\"o}lzke and Chris Power and Elina 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",

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

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

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Skaaby, T, Taylor, AE, Jacobsen, RK, Paternoster, L, Thuesen, BH, S. Ahluwalia, T, 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, MN, McSharry, C, Bonnelykke, K, Bisgaard, HF, Schulz, H, Strauch, K, Meitinger, T, Peters, A, Grallert, H, Nohr, EA, Kivimaki, M, Kumari, M, Völker, U, Nauck, M, Völzke, 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 consortiumn', Scientific Reports, vol. 7, no. 1, 2224. https://doi.org/10.1038/s41598-017-01977-w

TY - JOUR

T1 - Investigating the causal effect of smoking on hay fever and asthma: a Mendelian randomization meta-analysis in the CARTA consortiumn

AU - Skaaby, Tea

AU - Taylor, Amy E.

AU - Jacobsen, Rikke K.

AU - Paternoster, Lavinia

AU - Thuesen, Betina Heinsbæk

AU - S. Ahluwalia, Tarunveer

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 Eyrich

AU - McConnachie, Alex

AU - Sattar, Naveed

AU - Upton, Mark N.

AU - McSharry, Charles

AU - Bonnelykke, Klaus

AU - Bisgaard, Hans Flinker

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 - Hypponen, Elina

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

Y1 - 2017

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.

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 consortiumn

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