When complex phenotypes, like addiction phenotypes, display a polygenic genetic architecture it is unlikely that GWA studies lead to straightforward results that can be replicated in independent samples. The TAG meta-analyses showed that even with large samples sizes no genome-wide significant results were obtained for smoking initiation and age at smoking initiation. For CPD a very strong association was observed for the SNPs in the cluster of Nicotinic Receptor Genes on chromosome 15 (15q25.1) (38). This CPD phenotype was also responsible for significant results in the present study. Interestingly, the significant associations we observed were not driven by the top SNPs on chromosome 15. The association between the polygenic risk score for CPD and glasses alcohol or cannabis initiation was not significant when a smaller number of SNPs was selected, for example: Pt=.01 (data not shown). A recent study composed a polygenic risk score based on 4 of the top-SNPs from the 15q25.1 region and 2 SNPs from another region (19q13.2). This score was unrelated with smoking initiation, but the individuals with a high score were more likely to convert
