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[在理解精神疾病分子病因方面取得突破]

[Breakthrough in understanding the molecular causes of psychiatric disorders].

作者信息

Nöthen Markus M, Degenhardt Franziska, Forstner Andreas J

机构信息

Institut für Humangenetik, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland.

Zentrum für Humangenetik, Philipps-Universität Marburg, Baldingerstraße, 35033, Marburg, Deutschland.

出版信息

Nervenarzt. 2019 Feb;90(2):99-106. doi: 10.1007/s00115-018-0670-6.

Abstract

A long-established hypothesis is that genetic factors contribute to the development of psychiatric diseases, including common illnesses such as schizophrenia and the affective disorders; however, reliable molecular identification of these factors represents a far more recent innovation. This has been rendered possible by technological advances in the individual characterization of the human genome and the combining of large genetic datasets at the international level. For the first time, the results of genome-wide analyses provide researchers with systematic insights into disease-relevant biological mechanisms. Here, the integrated analysis of different omics level data generates important insights into the functional interpretation of the genetic findings. The results of genetic studies also demonstrated the degree of etiological overlap between differing psychiatric disorders, with the greatest commonality having been observed to date between schizophrenia and bipolar affective disorder. Although the translation of genetic findings into routine clinical practice is being pursued at various levels, elaborate follow-up studies are typically necessary. The diagnostic investigation of rare genomic deletions/duplications (so-called copy number variants) in patients with schizophrenia is likely to represent one of the first examples of routine clinical application. The necessary prerequisites for this are currently being defined.

摘要

一个长期存在的假说是,遗传因素促成了精神疾病的发展,包括精神分裂症和情感障碍等常见疾病;然而,对这些因素进行可靠的分子鉴定是一项更为近期的创新。人类基因组个体特征分析技术的进步以及国际层面大型遗传数据集的整合,使得这一切成为可能。全基因组分析的结果首次为研究人员提供了对疾病相关生物学机制的系统见解。在此,对不同组学水平数据的综合分析为遗传研究结果的功能解读带来了重要见解。遗传学研究结果还表明了不同精神疾病之间病因重叠的程度,迄今为止,精神分裂症和双相情感障碍之间的共性最为明显。尽管遗传研究结果在各个层面都在向常规临床实践转化,但通常还需要精心的后续研究。对精神分裂症患者罕见基因组缺失/重复(即所谓的拷贝数变异)进行诊断调查,可能是常规临床应用的首批实例之一。目前正在确定为此所需的先决条件。

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