DLGAP1 andNMDAreceptor‐associated postsynaptic density protein genes influence executive function in attention deficit hyperactivity disorder

Abstract

ObjectiveTo explore the association of DLGAP1 gene with executive function (EF) in attention deficit hyperactivity disorder (ADHD) children.MethodA 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.ResultsCompared with controls, children with ADHD showed poorer cognitive flexibility and inhibition. Two SNPs (rs2049161, p‐value = 5.08e‐7, adjusted p‐value = 1.63e‐4, rs16946051, p‐value = 5.18e‐7, adjusted p‐value = 1.66e‐4) survived multiple tests in Trail Making Test. Both SNPs also showed association with TOH (rs2049161, p = 6.82e‐4, rs16946051, p = 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 (p = .0057) and pathway level (p = .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.ConclusionChildren 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.

Epigenome-wide association of father’s smoking with offspring DNA methylation: a hypothesis-generating study

“…Two of the significant DMRs ( ATP6V1E1 and C2 ) and four of the top DMPs ( BCAS1 , MFGE8 , UNC93B1 , and RALB ) were annotated to genes related to innate and adaptive immunity and to different immune cell subsets (21–24, 31, 32). Furthermore, one DMR ( CTNNA2 ) and one DMP ( DLGAP1 ) mapped to genes involved in function and development of neuronal systems (25, 33), and to behavioural dysfunction (29, 34, 35).…”

Association of Gene Variations in Ionotropic Glutamate Receptor and Attention-Deficit/Hyperactivity Disorder in the Chinese Population: A Two-Stage Case–Control Study

“…As members of the iGluRs family, NMDAR and AMPAR dysfunction might be one of the potential causes of ADHD pathogenesis (J. P. Chang et al, 2014;Cheng et al, 2017;Fan et al, 2018;Medin et al, 2019), and GRID2 is critical for correcting NMDAR function and maintaining proper transmission of AMPAR signals (Kumagai et al, 2014;Yamasaki et al, 2011). In addition, dysfunction in GluRD2 is associated with a host of psychiatric phenotypes, including ASD, which shares 50%-70% of its contributing genetic factors with ADHD (Kalkan et al, 2016;Pinto et al, 2014;Rommelse et al, 2010), obsessive-compulsive disorder (OCD) (Khramtsova et al, 2019), and schizophrenia endophenotypes (Greenwood et al, 2016).…”

Neuropsychological characteristics of children with Attention-Deficit/Hyperactivity Disorder and Sluggish Cognitive Tempo

“…2) Trail Making Test (TMT) (Fan et al, 2018): the TMT contains two sections (sections A and B). Section A asked participants to draw lines to connect scattered numbered circles, while section B required the participants to alternately connect scattered encircled numbers and letters.…”

“…Any ADHD patients with an SCT score larger than or equal to 4 were grouped as ADHD patients with SCT (ADHD+SCT) (n = 58), and the other ADHD patients were grouped as ADHD patients without SCT (ADHD-SCT) (n = 480). 2) Trail Making Test (TMT) (Fan et al, 2018): the TMT contains two sections (sections A and B).…”

“…Those individuals with ADHD and SCT have higher levels of emotional and social problems and less externalizing behavior (Carlson & Mann, 2002;Ekinci et al, 2021). The presence of SCT in patients with ADHD often leads to more impaired social functioning (Ferretti et al, 2019).…”