Genetic analysis for cognitive flexibility in the trail-making test in attention deficit hyperactivity disorder patients from single nucleotide polymorphism, gene to pathway level.
Genetic analysis for cognitive flexibility in the trail-making test in attention deficit hyperactivity disorder patients from single nucleotide polymorphism, gene to pathway level.
复制标题
从单核苷酸多态性、基因到通路水平对注意力缺陷多动障碍患者的试验中的认知灵活性进行遗传分析。
DOI：
10.1080/15622975.2017.1386324
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Chang Suhua
中科院分区：
文献类型：
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作者：
Zhang Kunlin;Fan Zili;Wang Yufeng;Faraone Stephen V;Yang Li;Chang Suhua
目的：探讨注意缺陷多动障碍（ADHD）内表型的遗传基础，分析多基因小作用的通路，以期增加对ADHD遗传基础的认识。本研究旨在从单核苷酸多态性（SNP）、基因和通路水平探讨ADHD认知灵活性的遗传基础。方法：对788例ADHD患者进行认知灵活性测试。对644,166个snp进行了认知灵活性的全基因组关联分析。结果：在基因分析中，顶级SNP rs2049161 （P= 5.08 e-7）涉及基因DLGAP1和顶级基因CADPS2，导致大量文献证据表明其与精神疾病相关。基因表达和网络分析显示了它们对认知功能的贡献。间隔富集分析强调了“腺苷酸环化酶活性”和ADCY2对认知灵活性的潜在贡献。对所有snp的候选通路分析发现，谷氨酸系统、神经突生长和去甲肾上腺素能系统相关通路与认知灵活性显著相关（FDR< 0.05），其中神经突生长通路也与ADHD症状相关。结论：本研究为认知灵活性相关的基因和途径提供了证据，有助于揭示ADHD的遗传基础。
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= 5.08 e-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.