Association between the DAT1 gene and spatial working memory in attention deficit hyperactivity disorder

Abstract

An association between attention deficit hyperactivity disorder (ADHD) and the dopamine transporter gene (DAT1) was reported in clinical samples. This study aimed to explore whether there was an association between DAT1 and spatial working memory (SWM), a promising endophenotype for ADHD. This family-based association sample consisted of 382 probands with DSM-IV ADHD and their family members (n=1298) in Taiwan. The SWM task of the Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to measure SWM of all participants. We screened 15 polymorphisms across the DAT1 gene, including 14 single nucleotide polymorphisms (SNPs) and the variable number of tandem repeat polymorphism in the 3'-untranslated region. We used the Family-Based Association Test (FBAT) to test the associations of genetic polymorphisms with the SWM measures. In single locus association analyses, two SNPs (rs2617605 and rs37020) were significantly associated with the double errors (adjusted p=0.03 and 0.03, respectively) after adjustment for multiple testing. In haplotype analyses, a haplotype rs403636 (G)/rs463379 (C)/rs393795 (C)/rs37020 (G) was significantly associated with total within-search errors (minimal p=0.001), within-search errors in eight boxes (minimal p=0.002), total double errors (minimal p=0.001) and double errors in eight boxes (minimal p=0.004). Our finding of the haplotype rs403636 (G)/rs463379 (C)/rs393795 (C)/rs37020 (G) as a novel genetic marker for spatial working memory suggests that variation in DAT1 may provide insight into the pathways leading from genotype to phenotype of ADHD.