Markunas Christina A, Quinn Kaia S, Collins Ann L, Garrett Melanie E, Lachiewicz Ave M, Sommer Jennifer L, Morrissey-Kane Erin, Kollins Scott H, Anastopoulos Arthur D, Ashley-Koch Allison E
Center for Human Genetics, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Psychiatr Genet. 2010 Apr;20(2):73-81. doi: 10.1097/YPG.0b013e3283351209.
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.
先前已鉴定出一个家族，其3号染色体臂间倒位inv(3)(p14:q21)与一种早发性发育疾病共分离，该疾病的特征为冲动行为和智力缺陷。倒位断点分别位于p臂的DOCK3和q臂的SLC9A9内。基于此报告，在一项基于家族的注意力缺陷多动障碍（AD/HD）关联研究中选择对这些基因进行评估。
收集AD/HD症状的康纳斯父母（CPRS）和教师（CTRS）评定量表以及康纳斯连续作业测试（CPT）指标，并在每个基因中选择最少数量的标签单核苷酸多态性（SNP）进行分析。对符合AD/HD研究标准的家族进行分析。使用QTDT程序，根据CTRS和CPRS，对每个标签SNP与《精神疾病诊断与统计手册》第四版（DSM-IV）子量表的T分数以及五项CPT指标进行关联测试。
在进行多重检验校正后，SLC9A9的3'非翻译区中的一个SNP，rs1046706，根据CTRS与DSM-IV多动冲动和总症状子量表的分数以及CPT上的执行错误仍存在显著关联（错误发现率，q值<0.05）。此外，一个内含子SLC9A9 SNP，rs2360867，与执行错误仍存在显著关联。
我们的结果表明，SLC9A9可能与AD/HD中的多动冲动症状有关，SLC9A9的破坏可能是倒位家族中观察到的行为表型的原因。与SLC9A9的关联特别有趣，因为它最近在一项AD/HD全基因组关联研究中被牵连。有必要进一步研究SLC9A9在AD/HD和其他行为障碍中的作用。
