Genetic variants in SLC9A9 are associated with measures of attention-deficit/hyperactivity disorder symptoms in families.

Genetic variants in SLC9A9 are associated with measures of attention-deficit/hyperactivity disorder symptoms in families.
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DOI:
10.1097/ypg.0b013e3283351209
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发表时间:
2010-04
影响因子:
0.9
通讯作者:
Ashley-Koch AE
Ashley-Koch AE
中科院分区:
医学4区
文献类型:
--
作者:
Markunas CA;Quinn KS;Collins AL;Garrett ME;Lachiewicz AM;Sommer JL;Morrissey-Kane E;Kollins SH;Anastopoulos AD;Ashley-Koch AE

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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 singlenucleotide 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.