The evidence from animal experiments, treatment response and linkage study suggests that OPRM1 may be a gene contributing to the liability of tobacco smoking and nicotine dependence. In this study, we conduct association analyses to test whether the OPRM1 gene is associated with SI and ND. We use a 3-group design to compare the genotypic and allelic distribution of 11 SNPs between the non-smokers and regular smokers and that between the Low- and High-ND smokers. We find that three SNPs show genotypic associations with SI and only one SNP is associated with ND. In haplotype analyses, a core region covered by 3-marker combination 5-6-7 (rs9479757-rs2075572-rs10485057) reaches global significance for smoking initiation. A major haplotype, 1-2-1 or G-C-A, is overrepresented in the regular smokers as compared with the non-smokers. A minor haplotype for the same marker combination, 1-2-2 or G-C-G, is significantly associated with both SI and ND. Since the frequency of the minor haplotype is relatively low (0.013–0.026), there is a chance that this haplotype may be an artifact of the haplotype reconstruction program. It is well known that haplotypes
