Significant SNP associations with current smoking were seen in the case-control sample derived from MZ twins, but not when using a TDT-based analysis in the DZ sibling pairs. A reason for this may be the reduced power to detect association in the TDT framework when parental genotypes are missing and there is only one additional phenotyped (and genotyped) sibling (i.e. the DZ co-twin). Yang et al. (2003) demonstrated that for a common disease model, the absence of additional phenotyped siblings, affects power – this limitation could extend to our analyses of alcohol and illicit drug-related phenotypes as well. In addition, McGinnis et al. (2002) have argued that compared with the TDT (when including genotyped parents), case-control samples require fewer individuals to achieve a similar level of power – contrasting this with our TDT design, where parents are absent, it is plausible that the smaller case-control sample was sufficiently powered to detect the association signal. Notwithstanding these possibilities, our results with current smoking need careful replication and currently should be viewed with some caution. A number of emerging genomewide association studies
