Abstract

As a childhood-onset psychiatric disorder, attention deficit hyperactivity disorder (ADHD) is complicated by phenotypic and genetic heterogeneity. Lifelong executive function deficits in ADHD are described in many literatures and have been proposed as endophenotypes of ADHD. However, its genetic basis is still elusive. In this study, we performed a genome-wide association study of executive function, rated with Behavioral Rating Inventory of Executive Function (BRIEF), in ADHD children. We identified one significant variant (rs852004, P = 2.51e-08) for the overall score of BRIEF. The association analyses for each component of executive function found this locus was more associated with inhibit and monitor components. Further principle component analysis and confirmatory factor analysis provided an ADHD-specific executive function pattern including inhibit and monitor factors. SNP rs852004 was mainly associated with the Behavioral Regulation factor. Meanwhile, we found the significant locus was associated with ADHD symptom. The Behavioral Regulation factor mediated its effect on ADHD symptom. Functional magnetic resonance imaging (fMRI) analyses further showed evidence that this variant affected the activity of inhibition control related brain regions. It provided new insights for the genetic basis of executive function in ADHD.

Details

Title
Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder
Author
Sun, Xiao 1 ; Wu, Zhaomin 2 ; Cao, Qingjiu 1 ; Qian, Ying 1 ; Liu, Yong 3 ; Yang, Binrang 2 ; Chang, Suhua 4   VIAFID ORCID Logo  ; Yang, Li 1 ; Wang, Yufeng 1 

1  Peking University Sixth Hospital (Institute of Mental Health), National Clinical Research Center for Mental Disorders & Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China 
2  Shenzhen Children’s Hospital, Shenzhen, China 
3  CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China; College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, China 
4  CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China 
Pages
1-9
Publication year
2018
Publication date
May 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-26042-y
ProQuest document ID
2039832419
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.