Improving GWAS design through extension of phenotypic assessment could be done by taking characteristics into consideration that we already know or suspect to play a role in genetic susceptibility. Given the limits of the nosological systems, subdividing ADHD according to subtype will probably not be sufficient, as there is already evidence of shared genetic factors between subtypes (Faraone et al. 2000a; Thapar et al. 2006). Taking into account comorbidity might deal with some of the limits of the phenotypes, as a number of studies have suggested that ADHD plus a specific comorbidity may constitute a distinct subtype of ADHD (Faraone et al. 2000b; Faraone 2000; Faraone and Doyle 2001; Fliers et al. 2009; Rasmussen et al. 2004; Smalley et al. 2000; Willcutt et al. 2000). A recent study in IMAGE can be used as an example that this affects association findings: Zhou et al. (2008b) showed that SLC6A3/DAT1 was only associated with ADHD in the absence of conduct disorder. Another example is gender; given the difference between sexes, certain genetic risk factors can be expected to affect males and females
