Genetic influence on the age at onset of asthma: A twin study

Background: Although the genetics of asthma susceptibility have been frequently explored, little is known about genetic factors that influence the age at onset of asthma. Objective: To study the variation in the age at onset of asthma attributable to genetic and environmental factors. Methods: Data on the age at onset and predictors of asthma were collected in 2002 via a multidisciplinary questionnaire study of 34,782 Danish twins 20 to 71 years of age. Survival analytic methods were applied to partition variation in the age at onset of asthma into genetic and environmental components. Results: Sex, hay fever, atopic dermatitis, smoking, and exposure to passive smoking in childhood were significant risk factors, whereas BCG vaccination was protective for asthma. The risk of asthma in the co-twin of an affected twin was higher in monozygotic than in dizygotic twins (hazard ratio, 2.59; 95% CI, 1.83-3.68; P < .001). The risk of asthma in the co-twin decreased with increasing age at onset of asthma in the index twin (hazard ratio per ten years, 0.86; 95% CI, 0.76-0.98; P = .019). The effect was attenuated in dizygotic twins relative to monozygotic twins (P = .005). Genetic factors explained 34% of the variation in the age at onset of asthma, and environmental factors accounted for 66%. Conclusion: Host-related differences in genetic makeup cause different individuals to develop asthma at different ages. Better understanding of the causes for variation in the age at onset of disease may ultimately lead the way to targeted treatments. (J Allergy Clin Immunol 2010;126:626-30.)