Our approach to discovery of genes affecting AD and ND has both strengths and limitations. The main strength is that we have taken a joint approach to alcohol and nicotine dependence, which are known to have a partially overlapping genetic basis. This approach should allow the identification of common genes and mechanisms for AD and ND. A main limitation is that, for the Australian sample, a DNA-pooling approach was used. Although DNA-pooling is theoretically sound (Macgregor et al., 2006; Macgregor et al., 2008) and can produce important results at a low genotyping cost (Brown et al., 2008; Melquist et al., 2007; Papassotiropoulos et al., 2006; Spinola et al., 2007; Steer et al., 2007), it was necessary to discount data from SNPs with low minor allele frequency and poor signal-to-noise ratios which might have been captured in an individual-genotyping design. A 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
