A family was previously identified that cosegregates a pericentric inversion, inv(3)(p14 : q21), with an early-onset developmental condition, characterized by impulsive behavior and intellectual deficit. The inversion breakpoints lie within DOCK3 and SLC9A9 at the p-arm and q-arm, respectively. Based on this report, these genes were selected to be evaluated in a family-based attention-deficit/hyperactivity disorder (AD/HD) association study.
Conners' Parent (CPRS) and Teacher (CTRS) Rating Scales of AD/HD symptoms and Conners' Continuous Performance Test (CPT) measures were collected and a minimal number of tagging single-nucleotide polymorphisms (SNPs) in each gene were selected for analysis. Analyses were performed on families who met research criteria for AD/HD. Using the program, QTDT, each tagging SNP was tested for association with T-scores from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) subscales according to the CTRS and CPRS, and five CPT measures.
After adjusting for multiple testing, a SNP in the 3′ UTR of SLC9A9, rs1046706, remained significantly associated (false discovery rate, q value <0.05) with scores on the DSM-IV hyperactive-impulsive and total symptom subscales according to the CTRS and errors of commission on the CPT. In addition, an intronic SLC9A9 SNP, rs2360867, remained significantly associated with errors of commission.
Our results suggest that SLC9A9 may be related to hyperactive-impulsive symptoms in AD/HD and the disruption of SLC9A9 may be responsible for the behavioral phenotype observed in the inversion family. The association with SLC9A9 is particularly interesting as it was recently implicated in a genome-wide association study for AD/HD. Further investigation of the role of SLC9A9 in AD/HD and other behavioral disorders is warranted.
aCenter for Human Genetics, Department of Medicine
Departments of bPediatrics
cPsychology, Duke University Medical Center, Durham
dDepartment of Psychology, University of North Carolina, Greensboro, North Carolina, USA
Correspondence to Allison E. Ashley-Koch, PhD, Center for Human Genetics, Department of Medicine, Duke University Medical Center, 595 LaSalle, Box 3445, Durham, NC 27710, USA
Tel: +1 919 684 1805; fax: +1 919 684 0912;
Received 3 February 2009
Revised 29 August 2009
Accepted 13 September 2009