Release date: 2017-06-01
Recently, Wang Jing Research Group of the Institute of Psychology of the Chinese Academy of Sciences and the Wang Yufeng Research Group of the Sixth Hospital of Peking University and the Liu Dong Research Group of Peking University have conducted cooperation in patients with Attention deficit hyperactivity disorder (ADHD) in Chinese Han children. The first international genome-wide association study of ADHD to perform inhibitory functions and the discovery of new susceptibility genes associated with inhibition of ADHD implementation.
ADHD is a common behavioral disorder in children/adolescents with a prevalence of about 5%. It is mainly characterized by inattention, hyperactivity and impulsivity that are not commensurate with development. The pathogenesis of ADHD is still unclear and is generally considered to be a syndrome caused by a variety of biological, psychological and social factors. Currently, candidate gene association studies have found genes associated with disease, but these genes have only a 3.3% impact on disease phenotypic variation and can only account for 4.3% of heritability. At the same time, the disease has a complex phenotype and high heterogeneity, so no significant disease susceptibility genes have been found in the current genome-wide association studies.
Studies have shown that impaired executive function is a core defect in patients with ADHD. To gain a deeper understanding of the causes of ADHD, the researchers conducted the first two-stage GWAS study on the implementation of ADHD in the world, using the Stroop color-interference test to assess the inhibitory function of 1,702 cases, which was finally found on 7p22.3. A new susceptible site (rs11514810) that is significantly associated with the word interference time of the Stroop test.
At the same time, network analysis showed that most of the genes that interact with MICALL2 are associated with psychiatric disorders, while regulatory feature analysis and expression of quantitative trait locus (eQTL) data suggest that this site contributes to the expression of MICALL2 in the human brain.
In addition, the study found that by inhibiting the expression of zebrafish genes homologous to MICALL2, hyperactivity-impulsive behavior can be induced, which can be alleviated by the clinical drug of ADHD, atomoxetine, which further validates the gene. The pathogenic effect on ADHD.
The results suggest that MICALL2 is a novel susceptibility gene involved in the implementation of inhibitory defects in the hyperactive-impulsive behavior of ADHD, further emphasizing the possible role of neural development genes in the pathogenesis of ADHD. Execution inhibition plays an important role in the study of the pathogenesis of mental illness. This study, as the first GWAS study with a significant behavioral-cognitive phenotype, provides important information for the study of the genetic mechanisms of inhibition, and also shows Phenotypic perspectives will lead to new discoveries in the pathogenesis of ADHD.
This research is one of the series of results achieved by Wang Jing's research team in collaboration with clinical hospitals and the application of bioinformatics methods to explore the pathogenesis of complex diseases. Recently, relevant papers have been officially published in the journal Molecular Psychiatry.
The research was funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Beijing Municipal Science and Technology Commission.
Source: Institute of Psychology, Chinese Academy of Sciences
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