We observed a genotype-by-environment interaction between the risk of the rs8034191 genotype and current smoking status on COPD in the Norwegian sample (P = 0.002, Table 3), showing a substantially higher risk of COPD in current smokers carrying the rs8034191 C allele (OR = 2.0) than in former smokers (OR = 1.1). There are several possible explanations for this gene-by-environment interaction. First, it could relate to nicotine addiction; smokers that have greater difficulty quitting smoking may be more likely to develop COPD. Alternatively, it could indicate that a subset of individuals is at greater risk for developing COPD if they continue to smoke. A similar interaction with current smoking was not identified in the ICGN families. Since all the COPD patients in the NETT population were former smokers, we could not address this question in the NETT/NAS study.
