Objective-The main aim of this study was to examine the association between ADHDassociated genes and the course of ADHD.Methods-Subjects were derived from identically designed case-control family studies of boys and girls with ADHD and a genetic linkage study of families with children with ADHD. Caucasian probands and family members with ADHD and with available genetic data were included in this analysis (N=563). The course of ADHD was compared in subjects with and without putative risk alleles (DRD4 7-repeat allele, DAT1 10-repeat allele, and 5HTTLPR long © 2009 Elsevier Ireland Ltd. All rights reserved.Address correspondence to Joseph Biederman, MD, Clinical and Research Program in Pediatric, Psychopharmacology, Yawkey Center, Suite 6A, Massachusetts General Hospital, Boston, MA 02114. jbiederman@partners.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript allele). The persistence of ADHD (full or subthreshold diagnosis in the last month) was plotted using Kaplan-Meier survival functions and tested with Cox proportional hazard models.Results-Survival analyses revealed that by 25 years of age 76% of subjects with a DRD4 7-repeat allele were estimated to have persistent ADHD compared to 66% of subjects without the risk allele (hazard ratio=1.66, z=2.05, p=0.04). In contrast, there were no significant associations between the course of ADHD and the DAT1 10-repeat allele (p=0.94) and 5HTTLPR long allele (p=0.65).Conclusions-Our findings suggest that the DRD4 7-repeat allele is associated with a more persistent course of ADHD.