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.
Highlights
Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. 5The Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 6Steno Diabetes Center Copenhagen, Gentofte, 2820, Denmark. 7Research unit for Dietary Studies, the Parker Institute, Frederiksberg and Bispebjerg Hospitals, The Capital Region, Frederiksberg, Denmark. 8Centre for Population Health Research, School of Health Sciences and Sansom Institute of Health Research, University of South Australia, Adelaide, Australia. 9MRC Unit for Lifelong Health and Ageing at UCL, London, UK. 10K.G
For the Mendelian randomization analyses, the number of participants were for hay fever: N = 208,365, asthma: N = 231,013, and allergic sensitization: N = 17,623
We found a higher risk of asthma in former smokers compared with never smokers (OR = 1·11, 95% CI: 1·01, 1·21; P = 0·022), but not for current smokers (OR = 1·00, 95% CI: 0·91, 1·09; P = 0·967) (Fig. 1)
Summary
Allergic sensitization to inhalant allergens can be assessed by skin prick testing and/or measurements of serum specific IgE These are generally accepted objective markers of allergic respiratory disease that can be used both in clinical assessment and epidemiological studies. The rs16969968 SNP is in perfect linkage disequilibrium with rs1051730, and they are used interchangeably These genetic proxies for smoking, unlike smoking heaviness itself, are not associated with confounding factors that may distort associations with health outcomes, for example, socioeconomic status and education level[15]. To test the causal nature of the associations between smoking and hay fever, asthma, and allergic sensitization, we performed a Mendelian randomization meta-analysis combining data from 22 studies in the Causal Analysis Research in Tobacco and Alcohol (CARTA) consortium and the UK Biobank
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