We took into account the severity of COPD, reflected in the level of lung function, as a potential confounder when analyzing these two phenotypes. However, we hypothesize that additional factors such as frequency of exacerbations may also affect smoking behaviors in the COPD subjects that were studied here. Additionally, it is plausible that social factors, such as smoking trends changing over time, are important environmental determinants of smoking initiation and intensity, and they might have potentially confounded genetic associations found.
