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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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 languageEnglish
Article number2224
Number of pages9
JournalScientific Reports
Publication statusPublished - 22 May 2017


  • hay fever
  • asthma
  • smoking


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