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A new locus regulating MICALL2 expression was identified for association with executive inhibition in children with attention deficit hyperactivity disorder
Yang, L.1,2; Chang, S.3,4; Lu, Q.1,2; Zhang, Y.5; Wu, Z.1,2; Sun, X.1,2; Cao, Q.1,2; Qian, Y.1,2; Jia, T.6,7; Xu, B.6,7; Duan, Q.8; Li, Y.8,9,10; Zhang, K.; Schumann, G.6,7; Liu, D.11; Wang, J.3,4; Wang, Y.1,2; Lu, L.1,2
2018-04-01
Source PublicationMOLECULAR PSYCHIATRY
Correspondent Emailwangjing@psych.ac.cn
ISSN1359-4184
SubtypeArticle
Volume23Issue:4Pages:1014-1020
Contribution Rank2
Abstract

Impaired executive inhibition is a core deficit of attention deficit hyperactivity disorder (ADHD), which is a common childhoodonset 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.

DOI10.1038/mp.2017.74
Indexed BySCI ; SSCI
Language英语
Funding OrganizationMajor State Basic Research Development Program of China (973 Program)(2014CB846100) ; National Natural Science Foundation of China(31401139 ; Beijing Municipal Science and Technology Commission(Z151100003915122) ; National Institutes of Health(R01HL129132 ; Medical Research Council Grant 'c-VEDA' (Consortium on Vulnerability to Externalizing Disorders and Addictions)(MR/N000390/1) ; (695313) ; 81471381 ; R01HG006292) ; 31571496)
WOS Research AreaBiochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
WOS SubjectBiochemistry & Molecular Biology ; Neurosciences ; Psychiatry
WOS IDWOS:000428161500025
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS KeywordGENOME-WIDE ASSOCIATION ; JUNCTIONAL RAB13-BINDING PROTEIN ; DEFICIT/HYPERACTIVITY DISORDER ; RESPONSE-INHIBITION ; GENOTYPE IMPUTATION ; HEALTHY CONTROLS ; ADHD ; GENE ; VARIANTS ; NETWORK
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/26052
Collection中国科学院心理健康重点实验室
Affiliation1.Peking Univ, Hosp 6, Inst Mental Hlth, Natl Clin Res Ctr Mental Disorders, Beijing, Peoples R China
2.Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China
3.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China
5.Peking Univ, Coll Life Sci, Beijing, Peoples R China
6.Kings Coll London, Inst Psychiat, London, England
7.Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London, England
8.Univ N Carolina, Dept Genet, Chapel Hill, NC USA
9.Univ N Carolina, Dept Biostat, Chapel Hill, NC USA
10.Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA
11.Southern Univ Sci & Technol China, Dept Biol, Shenzhen, Guangdong, Peoples R China
Recommended Citation
GB/T 7714
Yang, L.,Chang, S.,Lu, Q.,et al. A new locus regulating MICALL2 expression was identified for association with executive inhibition in children with attention deficit hyperactivity disorder[J]. MOLECULAR PSYCHIATRY,2018,23(4):1014-1020.
APA Yang, L..,Chang, S..,Lu, Q..,Zhang, Y..,Wu, Z..,...&Lu, L..(2018).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.
MLA Yang, L.,et al."A new locus regulating MICALL2 expression was identified for association with executive inhibition in children with attention deficit hyperactivity disorder".MOLECULAR PSYCHIATRY 23.4(2018):1014-1020.
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