The interaction of genes and smoking on forced expiratory volume - A classic twin study

G J Zhai, A M Valdes, L Cherkas, G Clement, D Strachan, T D Spector

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20 Citations (Scopus)


Background: Genetic influences on lung function as measured by FEV1 have been reported from twin and family studies. The aims of this study were to estimate heritability of the ratio of measured FEV1 (mFEV(1)) to expected FEV1 (eFEV(1)) in a white population, and to examine the interaction between genetic factors and smoking on this ratio. Methods and subjects: The sample consisted of unselected monozygotic (MZ) and dizygotic (DZ) twin pairs from the TwinsUK registry. FEV1 was measured with a spirometer, and mFEV(1)/eFEV(1) ratio was calculated. Results: A total of 475 MZ and 1,054 DZ twin pairs participated (mean age, 47 years; range, 18 to 84 years). mFEV(1)/eFEV(1) ratio was 0.057 lower in smokers than nonsmokers (p <0.0001). The difference in the correlation for mFEV(1)/eFEV(1) ratio between MZ and DZ twin pairs was 0.32 in nonsmokers and 0.19 in current smokers, suggesting a significant genetic influence on lung function that was modified in current smokers. Using structural equation modeling, the heritability estimate for mFEV(1)/eFEV(1) ratio was found to be 66% (95% confidence interval [CI, 59 to 72%) in nonsmokers but significantly reduced to 32% (95% CI, 12 to 53%) in current smokers. However, there was no clear difference in the heritability of mFEVI/eFEV(1) ratio between nonsmokers and ex-smokers. Conclusion: Genes are the major influence on the variability of mFEV(1)/eFEV(1) ratio in nonsmokers. However, this strong genetic influence is strongly modified by an interaction with cigarettes
Original languageEnglish
Pages (from-to)1772 - 1777
Number of pages6
Issue number6
Publication statusPublished - Dec 2007


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