Collaborative analysis of DRD4 and DAT genotypes in populationdened ADHD subtypes

Background: It has been proposed that some of the variability in reporting of associations between attention deficit hyperactivity disorder (ADHD) and candidate genes may result from mixing of gen-etically heterogeneous forms of ADHD using DSM-IV criteria. The goal of the current study is to test whether population-based ADHD subtypes defined by latent class analysis help resolve issues of variable findings across individual gene association studies. Methods: Three studies which had pre-viously reported no associations between polymorphisms of the DRD4 and DAT genes and DSM-IV defined ADHD were reanalyzed using population-based and DSM-IV defined ADHD sub-types. Results: Across studies no significant associations were found for either DRD4 or DAT poly-morphisms using DSM-IV ADHD subtypes. In contrast, a significant association was found between the combined data set for the 440 base pair 3 ¢ DAT VNTR polymorphism and population-defined severe combined ADHD (OR 1.25, p .01). A marginally significant association was also found between the 7 repeat DRD4 allele and population-defined severe combined ADHD. Conclusion: Use of alternative population-based defined ADHD subtypes may help resolve some of the variable results presented for candidate gene association studies in ADHD. Keywords: Attention deficit/hyperactivity disorder, DRD4, DAT, latent class analysis. Abbreviations: ADHD: attention deficit/hyperactivity disorder