Progress in searching for susceptibility loci and genes for smoking-related behaviour

Smoking behaviour is influenced by both genetic and environmental factors. Many years of twin and adoption studies have demonstrated that heritability is at least 50% responsible for both smoking initiation and smoking persistence. Furthermore, the extent, to which genetic and environmental factors contribute to smoking behaviour, is significantly different in men and women. Linkage analyses from several independent studies provide evidences for suggested linkage of smoking behaviour to chromosomes 1, 2, 4, 5, 6, 9, 10, 11, 14, 17, 18 and 21. However, almost none of these loci have been replicated yet. Furthermore, numerous population-based association studies have been performed to examine the effects of a number of candidate genes, such as cytochrome P450, dopamine receptor (DR) and transporter, serotonin transporter and nicotinic acetylcholine receptor, on smoking behaviour. However, many of these reports have not yet received independent confirmation. Of these candidate genes, the D2 dopamine receptor (DRD2) gene has been extensively studied. Meta-analysis of 12 reported studies showed a significantly higher prevalence of the DRD2 TaqI A1 allele in smokers than that in non-smokers (p < 0.0001; pooled OR = 1.50; 95% CI = 1.33-1.70). For other candidate genes, insufficient published studies are available to allow a meta-analysis to be performed, or meta-analysis showed no significant difference between smokers and non-smokers. More studies are necessary to determine whether these genes play a significant role in smoking behaviour.