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全基因组关联研究结果:注意缺陷多动障碍的神经发育网络的鉴定。

Integrated genome-wide association study findings: identification of a neurodevelopmental network for attention deficit hyperactivity disorder.

机构信息

Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, the Netherlands.

出版信息

Am J Psychiatry. 2011 Apr;168(4):365-77. doi: 10.1176/appi.ajp.2010.10070948. Epub 2011 Feb 15.

Abstract

OBJECTIVE

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neuropsychiatric disorder. In the present study, the authors investigated the presence of genomic convergence in the top findings of the five published genome-wide association studies (GWASs) of ADHD.

METHOD

The authors carried out bioinformatics pathway analyses, using the Ingenuity and BiNGO tools, as well as a systematic literature analysis of 85 genes from the five published GWASs containing single nucleotide polymorphisms associated with ADHD at a p value <0.0001.

RESULTS

Findings revealed that 45 of the 85 top-ranked ADHD candidate genes encode proteins that fit into a neurodevelopmental network involved in directed neurite outgrowth. Data on copy number variations in patients with ADHD and data from animal studies provide further support for the involvement of this network in ADHD etiology. Several network proteins are also directly modulated by stimulants, the most commonly used psychopharmacological treatment for ADHD.

CONCLUSIONS

The authors have identified a protein network for ADHD that contributes to our understanding of the molecular basis of the disorder. In addition, the data suggest new candidate genes for ADHD and provide clues to future research into psychopharmacological ADHD treatments.

摘要

目的

注意缺陷多动障碍(ADHD)是一种高度遗传性神经精神疾病。在本研究中,作者研究了 ADHD 的五个已发表全基因组关联研究(GWAS)的顶级发现中存在的基因组趋同现象。

方法

作者使用 Ingenuity 和 BiNGO 工具进行了生物信息学途径分析,以及对包含与 ADHD 相关的单核苷酸多态性(p 值 <0.0001)的五个已发表的 GWAS 中的 85 个基因的系统文献分析。

结果

研究结果表明,85 个 ADHD 候选基因的前 45 个基因编码的蛋白质适合于涉及定向轴突生长的神经发育网络。ADHD 患者的拷贝数变异数据和动物研究数据为该网络参与 ADHD 病因学提供了进一步的支持。该网络的几个网络蛋白也被兴奋剂直接调节,兴奋剂是 ADHD 最常用的精神药理学治疗方法。

结论

作者确定了 ADHD 的蛋白质网络,有助于我们了解该疾病的分子基础。此外,这些数据还为 ADHD 的新候选基因提供了线索,并为未来的精神药理学 ADHD 治疗研究提供了线索。

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