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Genetic analysis for cognitive flexibility in the trail-making test in attention deficit hyperactivity disorder patients from single nucleotide polymorphism, gene to pathway level
Zhang, Kunlin1,2; Fan, Zili3,4; Wang, Yufeng3,4; Faraone, Stephen, V5,6,7; Yan, Li3,4; Chang, Suhua1,2
First AuthorKunlin Zhang
2019-07-03
Source PublicationWORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
Correspondent Emailsuhua chang changsh@psych.ac.cn ; li yang yangli_pkuimh@bjmu.edu.cn
ISSN1562-2975
Subtypearticle
Volume20Issue:6Pages:476-485
Contribution Rank1
Abstract

Objectives: Investigation of the genetic basis of endophenotype and analysis the pathways with multiple genes of small effects might increase the understanding of the genetic basis of attention deficit hyperactivity disorder (ADHD). Here we aimed to explore the genetic basis of cognitive flexibility in ADHD at the single nucleotide polymorphism (SNP), gene and pathway levels. Methods: The trail-making test was used to test the cognitive flexibility of 788 ADHD patients. A genome-wide association analysis of cognitive flexibility was conducted for 644,166 SNPs. Results: The top SNP rs2049161 (P = 5.08e-7) involved gene DLGAP1 and the top gene CADPS2 in the gene-based analysis resulted in much literature evidence of associations with psychiatric disorders. Gene expression and network analysis showed their contribution to cognition function. The interval-enrichment analysis highlighted a potential contribution of 'adenylate cyclase activity' and ADCY2 to cognitive flexibility. Candidate pathway-based analysis for all SNPs found that glutamate system-, neurite outgrowth- and noradrenergic system-related pathways were significantly associated with cognitive flexibility (FDR <0.05), among which the neurite outgrowth pathway was also associated with ADHD symptoms. Conclusions: This study provides evidence for the genes and pathways associated with cognitive flexibility and facilitate the uncovering of the genetic basis of ADHD.

KeywordAttention deficit hyperactivity disorder cognitive flexibility trail-making test genome-wide association study genetics
DOI10.1080/15622975.2017.1386324
Indexed BySCI
Language英语
WOS Research AreaPsychiatry
WOS SubjectPsychiatry
WOS IDWOS:000486211100006
PublisherTAYLOR & FRANCIS LTD
WOS KeywordCA2+-DEPENDENT ACTIVATOR PROTEIN ; GENOME-WIDE ASSOCIATION ; EXECUTIVE FUNCTION ; DEFICIT/HYPERACTIVITY DISORDER ; IDENTIFIES ASSOCIATION ; INDIVIDUAL-DIFFERENCES ; ENDOPHENOTYPE CONCEPT ; RESPONSE-INHIBITION ; ENRICHMENT ANALYSIS ; CANDIDATE GENES
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Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/29995
Collection中国科学院心理健康重点实验室
Corresponding AuthorYan, Li; Chang, Suhua
Affiliation1.Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China
2.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China
3.Peking Univ, Hosp 6, Inst Mental Hlth, Natl Clin Res Ctr Mental Disorders, Beijing, Peoples R China
4.Peking Univ, Key Lab Mental Hlth, Minist Hlth, Beijing, Peoples R China
5.SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA
6.SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA
7.Univ Bergen, KG Jebsen Ctr Res Neuropsychiat Disorders, Bergen, Norway
First Author AffilicationKey Laboratory of Mental Health, CAS
Corresponding Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Zhang, Kunlin,Fan, Zili,Wang, Yufeng,et al. Genetic analysis for cognitive flexibility in the trail-making test in attention deficit hyperactivity disorder patients from single nucleotide polymorphism, gene to pathway level[J]. WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY,2019,20(6):476-485.
APA Zhang, Kunlin,Fan, Zili,Wang, Yufeng,Faraone, Stephen, V,Yan, Li,&Chang, Suhua.(2019).Genetic analysis for cognitive flexibility in the trail-making test in attention deficit hyperactivity disorder patients from single nucleotide polymorphism, gene to pathway level.WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY,20(6),476-485.
MLA Zhang, Kunlin,et al."Genetic analysis for cognitive flexibility in the trail-making test in attention deficit hyperactivity disorder patients from single nucleotide polymorphism, gene to pathway level".WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY 20.6(2019):476-485.
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