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

Skaaby, Tea and Taylor, Amy E. and Jacobsen, Rikke K. and Paternoster, Lavinia and Thuesen, Betina H. and Ahluwalia, Tarunveer S. and Larsen, Sofus C. and Zhou, Ang and Wong, Andrew and Gabrielsen, Maiken E. and Bjorngaard, Johan H. and Flexeder, Claudia and Mannisto, Satu and Hardy, Rebecca and Kuh, Diana and Barry, Sarah J. and Mollehave, Line Tang and Cerqueira, Charlotte and Friedrich, Nele and Bonten, Tobias N. and Noordam, Raymond and Mook-Kanamori, Dennis O. and Taube, Christian and Jessen, Leon E. and McConnachie, Alex and Sattar, Naveed and Upton, Mark and McSharry, Charles and Bonnelykke, Klaus and Bisgaard, Hans and Schulz, Holger and Strauch, Konstantin and Meitinger, Thomas and Peters, Annette and Grallert, Harald and Nohr, Ellen A. and Kivimaki, Mika and Kumari, Meena and Volker, Uwe and Nauck, Matthias and Volzke, Henry and Power, Chris and Hypponen, Elena and Hansen, Torben and Jorgensen, Torben and Pedersen, Oluf and Salomaa, Veikko and Grarup, Niels and Langhammer, Arnulf and Romundstad, Pal R. and Skorpen, Frank and Kaprio, Jaakko and Munafo, Marcus R. and Linneberg, Allan (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. ISSN 2045-2322 (

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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.


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