Interaction between smoking and genetic factors in the development of chronic bronchitis

Abstract

Rationale: Smoking is a primary risk factor for chronic bronchitis, emphysema, and chronic obstructive pulmonary disease, but since not all smokers develop disease, it has been suggested that some individuals may be more susceptible to exogenous factors, such as smoking, and that this susceptibility could be genetically determined.

Objectives: The aim of the present study was to assess, in a population-based sample of twins, the following: (1) to what extent genetic factors contribute to the development of chronic bronchitis, including emphysema, taking sex into consideration, and (2) whether the genetic influences on chronic bronchitis, including emphysema, are separate from those for smoking behavior.

Methods: Disease cases and smoking habits were identified in 44,919 twins older than 40 years from the Swedish Twin Registry. Disease was defined as self-reported chronic bronchitis or emphysema, or recurrent cough with phlegm. Individuals who had smoked 10 pack-years or more were defined as smokers. Univariate and bivariate structural equation models were used to estimate the heritability specific for chronic bronchitis and that in common with smoking.

Measurements and main results: The heritability estimate for chronic bronchitis was a moderate 40% and only 14% of the genetic influences were shared with smoking.

Conclusions: Genetic factors independent of those related to smoking habits play a role in the development of chronic bronchitis.

Figure 1.

Bivariate path diagram describing the genetic (A) and nonshared environmental (E) effects that are common to smoking and chronic bronchitis, as well as the genetic and nonshared environmental effects that are unique to each phenotype, adjusted for prevalence differences related to age and sex. The observed traits (smoking and chronic bronchitis) are represented by rectangles, whereas unobserved (latent) genetic and nonshared environmental variables are represented by circles. The parameter estimates (arrows) are path coefficients, indicating the relative importance of the latent variables A and E to smoking and chronic bronchitis. The square of these estimates represents the variance of the trait accounted for by that specific latent factor. *Common genetic path.