title: A haplotype of the norepinephrine transporter gene (SLC6A2) is associated with visual memory in attention-deficit/hyperactivity disorder.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is a common heritable childhood-onset psychiatric disorder with impaired visual memory. Based on the evidence from treatment effect of atomoxetine, which interacts directly with the norepinephrine transporter, on visual memory in children with ADHD, this study examined the linkage disequilibrium structure of the norepinephrine transporter gene (SLC6A2) and the association between SLC6A2 and ADHD and visual memory, 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 total) of Han Chinese in Taiwan. Visual memory was assessed by the Pattern Recognition Memory (PRM) and Spatial Recognition Memory (SRM) tasks of the Cambridge Neuropsychological Test Automated Battery (CANTAB). We screened 21 polymorphisms across SLC6A2 and used the Family-Based Association Test (FBAT) to test the associations of SLC6A2 polymorphisms with ADHD and the PRM and SRM measures. In haplotype analyses, a haplotype rs36011 (T)/rs1566652 (G) was significantly associated with ADHD (minimal p=0.045) after adjustment for multiple testing. In quantitative analyses, this TG haplotype also demonstrated significant associations with visual memory measures, including mean latency of correct responses in PRM (minimal p=0.019), total correct responses in PRM (minimal p=0.018), and total correct responses in SRM (minimal p=0.015). Our novel finding of the haplotype rs36011 (T)/rs1566652 (G) as a novel genetic marker involved in both ADHD disease susceptibility and visual memory suggests that allelic variations in SLC6A2 could provide insight into the pathways leading from genotype to phenotype of ADHD.
authors.affiliation: Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chi-Yung
authors.initials: CY
authors.lastname: Shang
authors.affiliation: Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Huey-Ling
authors.initials: HL
authors.lastname: Chiang
authors.affiliation: Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Brain and Mind Sciences and Clinical Medicine, National Taiwan University, Taipei, Taiwan. Electronic address: gaushufe@ntu.edu.tw.
authors.forename: Susan Shur-Fen
authors.initials: SS
authors.lastname: Gau
mesh_terms: D044466:Asian People / Q000235:genetics; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology*; D002648:Child; D002681:China / Q000208:ethnology; D058068:Endophenotypes; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008568:Memory; D009483:Neuropsychological Tests; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011930:Reaction Time / Q000235:genetics; D013624:Taiwan; D014796:Visual Perception / Q000235:genetics*
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; C493227:SLC6A2 protein, human
keywords: Attention-deficit/hyperactivity disorder; Endophenotype; Haplotype; Norepinephrine transporter gene; Visual memory