Taken together, results from this study follow the pattern of complexity typically observed for psychiatric genetics, which is illustrative of how both genetic diversity (ethnic differences) and phenotypic heterogeneity (co-morbidity with other disorders) makes it difficult to interpret non-replications. In the CADD sample, we found suggestive evidence of associations between genetic variation in CHRNA4 and lifetime DSM-IV ND symptoms, but this result must be interpreted with caution. Since the results did not replicate in the GADD, which is phenotypically quite similar, it is not clear whether this represents a true non-replication or if it is due to reduced sample size and statistical power. It is encouraging that the nominal associations reported here are consistent and replicate prior results with CHRNA4 in separate samples. In conclusion, this work adds to the emerging literature exploring the role of these genes in smoking-related behaviors, suggesting that the common α4β2* nicotinic receptors remain an important possible target for pharmacogenetic therapies.
