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Mol Psychiatry. 2018 Apr;23(4):1014-1020. doi: 10.1038/mp.2017.74. Epub 2017 Apr 18.

A new locus regulating MICALL2 expression was identified for association with executive inhibition in children with attention deficit hyperactivity disorder.

Yang L1, Chang S2,3, Lu Q1, Zhang Y4, Wu Z1, Sun X1, Cao Q1, Qian Y1, Jia T5,6, Xu B5,6, Duan Q7, Li Y7,8,9, Zhang K2, Schumann G5,6, Liu D10, Wang J2,3, Wang Y1, Lu L1.

Author information

Peking University Sixth Hospital (Institute of Mental Health), National Clinical Research Center for Mental Disorders and Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China.
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
College of Life Science, Peking University, Beijing, China.
Institute of Psychiatry, King's College London, London, UK.
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA.
Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA.
Department of Biology, Southern University of Science and Technology of China, Guangdong, China.


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.

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