Linkage of attention deficit hyperactivity disorder (ADHD) to the short arm-centromeric region of chromosome 5 has been reported in multiple studies. The overlapping region (5p13-q11) contains a number of strong candidate genes for ADHD, based on their role in brain function or neurodevelopment. The aim of this study was to investigate some of the top candidates among these genes in relation to ADHD in a sample of 245 nuclear families from the Toronto area. We investigated the genes for the glial cell-derived neurotropic factor (GDNF), the fibroblast growth factor 10 (FGF10), islet-1 (ISL1), the hyperpolarized potassium channel (HCN1) and the integrin alpha 1 (ITGA1). In addition to these genes, we assessed the 3'region of the SLC1A3 gene, a glutamate transporter implicated in ADHD by a previous association study. A total of 36 polymorphisms were selected across the six genes. We performed family-based association and haplotype analyses. ADHD is a dimensional disorder, with symptoms of inattention and hyperactivity-impulsivity therefore, we also conducted quantitative analysis in relation to symptom scores for both dimensions. Single marker and haplotype analyses yielded little evidence of association for any of the genes tested in this study. Moreover, we were unable to replicate the positive association findings reported for SLC1A3. Our results suggest that these six genes are unlikely to be susceptibility genes in the chromosome 5p13-q11 region and other genes should now be considered for priority study.
Copyright 2007 Wiley-Liss, Inc.