Peking University Sixth Hospital (Institute of Mental Health) National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health Ministry of Health (Peking University) Beijing China.
CAS Key Laboratory of Mental Health Institute of Psychology Beijing China.
Brain Behav. 2018 Jan 23;8(2):e00914. doi: 10.1002/brb3.914. eCollection 2018 Feb.
To explore the association of DLGAP1 gene with executive function (EF) in attention deficit hyperactivity disorder (ADHD) children.
A total of 763 ADHD children and 140 healthy controls were enrolled. The difference of EF between ADHD and controls was analyzed using the analysis of covariance (ANCOVA), with IQ, sex, and age as covariates. Both the associations of SNPs with EF and three symptom traits of ADHD were conducted using an additive linear regression model by PLINK with the same covariates as ANCOVA.
Compared with controls, children with ADHD showed poorer cognitive flexibility and inhibition. Two SNPs (rs2049161, -value = 5.08e-7, adjusted -value = 1.63e-4, rs16946051, -value = 5.18e-7, adjusted -value = 1.66e-4) survived multiple tests in Trail Making Test. Both SNPs also showed association with TOH (rs2049161, = 6.82e-4, rs16946051, = 7.91e-4). Set-based analysis for gene DLGAP1 and its functional pathway DLGAP1-DLG4-NMDA showed they were associated with cognitive flexibility at both gene ( = .0057) and pathway level ( = .0321). Furthermore, the gene and pathway also showed association with ADHD symptom score. The associated SNPs and their LD proxies were related to the expression of DLGAP1 in medulla and frontal cortex.
Children with ADHD showed deficit in EF, especially, cognitive flexibility and inhibition. DLGAP1 was associated with cognitive flexibility and plan, and the role of DLGAP1 might be implemented through the complex of DLGAP1-DLG4-NMDA.
探讨 DLGAP1 基因与注意缺陷多动障碍（ADHD）儿童执行功能（EF）的关系。
共纳入 763 名 ADHD 患儿和 140 名健康对照。采用协方差分析（ANCOVA）比较 ADHD 组与对照组 EF 的差异，以智商（IQ）、性别和年龄为协变量。采用 PLINK 软件的加性线性回归模型，以与 ANCOVA 相同的协变量，分析 SNP 与 EF 及 ADHD 三个症状特征的关系。
与对照组相比，ADHD 患儿的认知灵活性和抑制能力较差。在连线测试中，有 2 个 SNP（rs2049161，-value=5.08e-7，调整后的 -value=1.63e-4，rs16946051，-value=5.18e-7，调整后的 -value=1.66e-4）在多次检验中均具有统计学意义。这两个 SNP 与 TOD 也具有相关性（rs2049161， =6.82e-4，rs16946051， =7.91e-4）。DLGAP1 基因及其功能途径 DLGAP1-DLG4-NMDA 的基于集合的分析表明，它们在基因（ =0.0057）和途径水平（ =0.0321）上均与认知灵活性相关。此外，该基因和途径也与 ADHD 症状评分相关。相关 SNP 及其 LD 近交系与延髓和前额皮质中 DLGAP1 的表达有关。
ADHD 患儿的 EF 存在缺陷，特别是认知灵活性和抑制能力。DLGAP1 与认知灵活性和计划有关，其作用可能是通过 DLGAP1-DLG4-NMDA 复合物来实现的。
