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Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder

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 bas...

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Autores principales: Sun, Xiao, Wu, Zhaomin, Cao, Qingjiu, Qian, Ying, Liu, Yong, Yang, Binrang, Chang, Suhua, Yang, Li, Wang, Yufeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956073/
https://www.ncbi.nlm.nih.gov/pubmed/29769613
http://dx.doi.org/10.1038/s41598-018-26042-y
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author Sun, Xiao
Wu, Zhaomin
Cao, Qingjiu
Qian, Ying
Liu, Yong
Yang, Binrang
Chang, Suhua
Yang, Li
Wang, Yufeng
author_facet Sun, Xiao
Wu, Zhaomin
Cao, Qingjiu
Qian, Ying
Liu, Yong
Yang, Binrang
Chang, Suhua
Yang, Li
Wang, Yufeng
author_sort Sun, Xiao
collection PubMed
description 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.
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spelling pubmed-59560732018-05-21 Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder Sun, Xiao Wu, Zhaomin Cao, Qingjiu Qian, Ying Liu, Yong Yang, Binrang Chang, Suhua Yang, Li Wang, Yufeng Sci Rep Article 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. Nature Publishing Group UK 2018-05-16 /pmc/articles/PMC5956073/ /pubmed/29769613 http://dx.doi.org/10.1038/s41598-018-26042-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sun, Xiao
Wu, Zhaomin
Cao, Qingjiu
Qian, Ying
Liu, Yong
Yang, Binrang
Chang, Suhua
Yang, Li
Wang, Yufeng
Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder
title Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder
title_full Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder
title_fullStr Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder
title_full_unstemmed Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder
title_short Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder
title_sort genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956073/
https://www.ncbi.nlm.nih.gov/pubmed/29769613
http://dx.doi.org/10.1038/s41598-018-26042-y
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