second limitation is the comparatively small sample size, although we estimate that power would be adequate to detect variants accounting for about 1–2% of variation in liability to AD or ND. Furthermore, we attempted to replicate the Australian results in another population with data available for both alcohol- and nicotine- dependence-related phenotypes. The lack of reproducible results on SNP level reinforces the view that genetic risk of AD or ND arises from multiple polymorphisms of individually small effect. Other published genomewide association studies of AD or ND have similarly found a paucity of large effects (e.g., Bierut et al., 2007; Treutlein et al., 2009). A third limitation of the current meta-analysis was the difference in dependence definitions in the three samples. Nicotine dependence was assessed using DSM-IV criteria for lifetime ND in the Australian sample and for FTND criteria in both Dutch samples. Alcohol dependence was defined as DSM-IV lifetime AD in the Australian and NESDA samples whereas the broader CAGE criteria were used in the NTR sample. A fourth limitation may be that specific genetic effects on AD may be harder to detect as it is much more likely to be comorbid with ND than vice versa. For instance
