PUBLICATION
A new locus regulating MICALL2 expression was identified for association with executive inhibition in children with attention deficit hyperactivity disorder
- Authors
- Yang, L., Chang, S., Lu, Q., Zhang, Y., Wu, Z., Sun, X., Cao, Q., Qian, Y., Jia, T., Xu, B., Duan, Q., Li, Y., Zhang, K., Schumann, G., Liu, D., Wang, J., Wang, Y., Lu, L.
- ID
- ZDB-PUB-170419-4
- Date
- 2017
- Source
- Molecular psychiatry 23(4): 1014-1020 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Asian People/genetics
- Atomoxetine Hydrochloride/pharmacology
- Attention Deficit Disorder with Hyperactivity/genetics*
- Attention Deficit Disorder with Hyperactivity/metabolism
- Attention Deficit Disorder with Hyperactivity/prevention & control
- Brain/pathology
- Child
- China
- Chromosomes, Human, Pair 7
- Ethnicity/genetics
- Executive Function
- Female
- Gene Expression
- Genome-Wide Association Study
- Humans
- Impulsive Behavior
- Male
- Microfilament Proteins/biosynthesis
- Microfilament Proteins/genetics*
- Neuropsychological Tests
- Phenotype
- Quantitative Trait Loci
- Zebrafish
- PubMed
- 28416812 Full text @ Mol. Psychiatry
Citation
Yang, L., Chang, S., Lu, Q., Zhang, Y., Wu, Z., Sun, X., Cao, Q., Qian, Y., Jia, T., Xu, B., Duan, Q., Li, Y., Zhang, K., Schumann, G., Liu, D., Wang, J., Wang, Y., Lu, L. (2017) A new locus regulating MICALL2 expression was identified for association with executive inhibition in children with attention deficit hyperactivity disorder. Molecular psychiatry. 23(4):1014-1020.
Abstract
Impaired executive inhibition is a core deficit of attention deficit hyperactivity disorder (ADHD), which is a common childhood-onset psychiatric disorder with high heritability. In this study, we performed a two-stage genome-wide association study of executive inhibition in ADHD in Han Chinese. We used the Stroop color-word interference test to evaluate executive inhibition. After quality control, 780 samples with phenotype and covariate data were included in the discovery stage, whereas 922 samples were included in the replication stage. We identified one new significant locus at 7p22.3 for the Stroop word interference time (rs11514810, P=3.42E-09 for discovery, P=0.01176 for replication and combined P=5.249E-09). Regulatory feature analysis and expression quantitative trait loci (eQTL) data showed that this locus contributes to MICALL2 expression in the human brain. Most genes in the network interacting with MICALL2 were associated with psychiatric disorders. Furthermore, hyperactive-impulsive-like behavior was induced by reducing the expression of the zebrafish gene that is homologous to MICALL2, which could be rescued by tomoxetine (atomoxetine), a clinical medication for ADHD. Our results suggested that MICALL2 is a new susceptibility gene for executive inhibition deficiency related to hyperactive-impulsive behavior in ADHD, further emphasizing the possible role of neurodevelopmental genes in the pathogenic mechanism of ADHD.Molecular Psychiatry advance online publication, 18 April 2017; doi:10.1038/mp.2017.74.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping