Although there is evidence of association of CHRNA 3/5 locus with nicotine addiction, both this study and recent reports of a lung cancer association [12]–[14] with the same alleles suggest that this region may be involved in more than nicotine addiction, and may potentially have direct functional relevance in the development of COPD, lung cancer, peripheral arterial disease, and other smoking related conditions. This evidence concerns the gene CHRNA1 and nicotine dependence.