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自杀行为的遗传学根源?关于证据多样性、疾病特异性和神经发育性脑转录组学的自杀行为相关基因概述。

Genetic origins of suicidality? A synopsis of genes in suicidal behaviours, with regard to evidence diversity, disorder specificity and neurodevelopmental brain transcriptomics.

机构信息

National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Karolinska Institute (KI), Stockholm, Sweden.

National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Karolinska Institute (KI), Stockholm, Sweden; WHO collaborating Centre for research, methods, development and training in suicide prevention, Sweden.

出版信息

Eur Neuropsychopharmacol. 2020 Aug;37:1-11. doi: 10.1016/j.euroneuro.2020.06.002. Epub 2020 Jul 4.

DOI:10.1016/j.euroneuro.2020.06.002
PMID:32636053
Abstract

With regard to suicidal behavior (SB) genetics, many novel genes have been implicated over the years, in particular by a variety of hypothesis-free genomic methods (e.g. GWAS and exome sequencing). In addition, many novel SB gene findings appear enigmatic in their biological relevance and have weak statistical support, e.g. lack direct replications. Adding to this is the comorbidity between psychiatric disorders and SB. Here we provide a synopsis of SB genes, by prioritization of 106 (out of ~2500) genes based on their highest level of evidence diversity across mainly five genetic evidence types (candidate/GWAS SNP, CNV, linkage and whole exome sequencing), supplemented by three functional categories. This is a representative set of both old and new SB gene candidates, implicated by all kinds of evidence. Furthermore, we define a subset of 40 SB "specific" genes, which are not found among ~3900 genes implicated in other neuropsychiatric disorders, e.g. Autism spectrum disorders (ASD) or Schizophrenia. Biological research of suicidality contains a major developmental focus, e.g. with regard to the gene-environment interactions and epigenetic effects during childhood. Less is known about early (fetal) development and SB genes. Inspired by huge efforts to understand the role early (fetal) neurodevelopment in e.g. ASD by using brain transcriptomic data, we here also characterize the 106 SB genes. We find interesting spatiotemporal expression differences and similarities between SB specific and non-specific genes during brain neurodevelopment. These aspects are of interest to investigate further, to better understand and counteract the genetic origins suicidality.

摘要

关于自杀行为(SB)遗传学,多年来已经有许多新的基因被涉及,特别是通过各种无假设的基因组方法(例如 GWAS 和外显子组测序)。此外,许多新的 SB 基因发现其生物学相关性似乎很神秘,并且统计支持较弱,例如缺乏直接的复制。此外,精神疾病和 SB 之间存在共病现象。在这里,我们根据主要的五种遗传证据类型(候选/GWAS SNP、CNV、连锁和全外显子组测序)对 106 个(约 2500 个)基因进行了优先级排序,提供了一个 SB 基因概要,根据它们的证据多样性水平进行排序,辅以三个功能类别。这是一组既有旧候选基因,也有新候选基因的代表集合,这些基因都与各种证据有关。此外,我们定义了 40 个 SB“特定”基因的子集,这些基因在约 3900 个与其他神经精神疾病(例如自闭症谱系障碍(ASD)或精神分裂症)相关的基因中找不到。自杀性的生物学研究包含一个主要的发育重点,例如,关于儿童时期的基因-环境相互作用和表观遗传效应。关于早期(胎儿)发育和 SB 基因的了解较少。受通过使用大脑转录组数据来理解早期(胎儿)神经发育在 ASD 中的作用的巨大努力的启发,我们在这里还对 106 个 SB 基因进行了特征描述。我们发现了 SB 特异性和非特异性基因在大脑神经发育过程中有趣的时空表达差异和相似性。这些方面值得进一步研究,以更好地理解和对抗自杀的遗传根源。

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