RESEARCH ARTICLE An Association Between a Dopamine Transporter Gene (SLC6A3) Haplotype and ADHD Symptom Measures in Nonclinical Adults Janette H.S. Tong,* Tarrant D.R. Cummins,* Beth P. Johnson, Leigh-Anne McKinley, Hayley E. Pickering, Peter Fanning, Nicole R. Stefanac, Daniel P. Newman, Ziarih Hawi, and Mark A. Bellgrove Monash University, School of Psychological Sciences, Melbourne, Victoria, Australia Manuscript Received: 6 October 2014; Previous genetic studies have postulated that attention deficit hyperactivity disorder (ADHD) should be regarded as the extreme end of a set of behavioural traits that can be continu- ously measured in the general population. The current study adopted a quantitative trait approach to examine the relation- ship between dopamine gene variants and self-reported ADHD symptoms in 517 nonclinical adults. Although genetic associa- tions with variants of both the dopamine transporter (DAT1; SLC6A3) and D4 receptor (DRD4) genes have been reliably reported in children, results in adults are less consistent. We probed two potentially functional variable number of tandem repeat (VNTR) polymorphisms in the 3 0 UTR and intron 8 of DAT1, the 10-repeat and 6-repeat alleles of which respectively form a haplotype (10/6 DAT1 haplotype) that is associated with childhood ADHD. We also genotyped the exon 3 VNTR of DRD4, the 7-repeat allele of which is also an established risk factor for childhood ADHD. Permutation analysis showed an influence of the 10/6 DAT1 haplotype on both CAARS-G and CAARS-H (DSM-IV ADHD Symptoms Total and ADHD Index respective- ly), such that ADHD symptom scores increased with each additional copy of the 10/6 DAT1 haplotype. This result survived corrections for multiple comparisons both at the level of genotype and phenotype. A nominal association with CAARS-G was also found for the 7-repeat allele of the DRD4 VNTR however this did not survive multiple comparison correction. Our results provide further support for the influence of variation in the 10/6 DAT1 haplotype and individual differences in ADHD symptoms in adults. Ó 2015 Wiley Periodicals, Inc. Key words: DAT1; DRD4; CAARS; quantitative trait INTRODUCTION Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition that is characterized by inattention, hyperactivity and impulsivity. ADHD affects 3–6% of school age children worldwide with symptoms continuing into adulthood in 5–66% of these cases such that there is an estimated worldwide- pooled prevalence rate of 5.29–7.1% [Barkley et al., 2002; Polanczyk et al., 2007; Willcutt et al., 2012; Polanczyk et al., 2014]. An estimated heritability for ADHD of 0.7–0.9 has been reported across familial, twin and adoption studies indicating that common genetic variations within ADHD-associated candidate genes are likely to be an important factor underlying the ADHD phenotype [Gillis et al., 1992; Stevenson, 1992; Gjone et al., 1996; Levy et al., 1997]. It has been hypothesized that the inattention and hyperac- tivity that is characteristic of ADHD arises in part from impaired dopaminergic transmission and in particular from excessive syn- aptic reuptake of dopamine [Levy, 1991]. Genetic, pharmacologi- cal, animal and brain imaging studies support this proposal and How to Cite this Article: Tong JHS,Cummins TDR, Johnson BP, McKinley L-A, Pickering HE, Fanning P, Stefanac NR, Newman DP, Hawi Z, Bellgrove MA. 2015. An Association Between a Dopamine Transporter Gene (SLC6A3) Haplotype and ADHD Symptom Measures in Nonclinical Adults. Am J Med Genet Part B. 9999:1–8. Conflict of Interest: MAB received remuneration for speaking and travel expenses from Lilly Pharmaceuticals, MAB reports no further conflicts of interest. J.H.S.T., T.D.R.C., B.P.J., L.M., H.E.P., P.F., N.R.S., D.P.N., Z.H., report no conflicts of interest. The material presented in the accompanying manuscript is original research, it has not been previously published and has not been submitted for publication elsewhere while under consideration. Janette H.S. Tong and Tarrant D.R. Cummins contributed equally to this work.  Correspondence to: Professor Mark A. Bellgrove, PhD, School of Psychological Sciences, Monash University, Melbourne 3800, Victoria, Australia. E-mail: mark.bellgrove@monash.edu Article first published online in Wiley Online Library (wileyonlinelibrary.com): 00 Month 2015 DOI 10.1002/ajmg.b.32283 Ó 2015 Wiley Periodicals, Inc. 1 Neuropsychiatric Genetics