Genetic architecture for human aggression: A study of gene-phenotype relationship in OMIM.
Genetic architecture for human aggression: A study of gene-phenotype relationship in OMIM.
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人类攻击性的遗传结构：OMIM 中基因-表型关系的研究。
DOI：
10.1002/ajmg.b.32363
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Faraone,StephenV
中科院分区：
文献类型：
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作者：
Zhang-James,Yanli;Faraone,StephenV
人类攻击的遗传研究主要集中在已知的候选基因和调节血清素和多巴胺信号和激素功能的途径上。这些研究让我们对人类攻击性的遗传学有了更多的了解，但还没有一个基因位点具有基因组意义。我们在此提出一项基于一个矛盾假设的综述，即对罕见的功能性遗传变异的研究可以更好地理解复杂的多因素疾病（如攻击）的分子机制。我们检查了人类基因和遗传疾病在线目录——人类孟德尔在线遗传（OMIM）中列出的所有攻击表型。我们确定了95种人类疾病，这些疾病至少在一个具有明确定义的遗传变异的个体中有侵略性症状。我们总共检索了86个致病基因。虽然这些基因中的大多数在以前的研究中没有涉及到人类的攻击行为，但最显著富集的典型途径在以前与攻击行为有关（例如，血清素和多巴胺信号）。我们的发现提供了强有力的证据来支持这些途径在攻击发病机制中的因果作用。此外，我们发现的新基因和途径暗示了人类攻击起源的其他机制。需要进行大样本的全基因组关联研究，以确定这些基因中的常见变异是否是攻击的危险因素。©2015 Wiley期刊公司
Genetic studies of human aggression have mainly focused on known candidate genes and pathways regulating serotonin and dopamine signaling and hormonal functions. These studies have taught us much about the genetics of human aggression, but no genetic locus has yet achieved genome‐significance. We here present a review based on a paradoxical hypothesis that studies of rare, functional genetic variations can lead to a better understanding of the molecular mechanisms underlying complex multifactorial disorders such as aggression. We examined all aggression phenotypes catalogued in Online Mendelian Inheritance in Man (OMIM), an Online Catalog of Human Genes and Genetic Disorders. We identified 95 human disorders that have documented aggressive symptoms in at least one individual with a well‐defined genetic variant. Altogether, we retrieved 86 causal genes. Although most of these genes had not been implicated in human aggression by previous studies, the most significantly enriched canonical pathways had been previously implicated in aggression (e.g., serotonin and dopamine signaling). Our findings provide strong evidence to support the causal role of these pathways in the pathogenesis of aggression. In addition, the novel genes and pathways we identified suggest additional mechanisms underlying the origins of human aggression. Genome‐wide association studies with very large samples will be needed to determine if common variants in these genes are risk factors for aggression. © 2015 Wiley Periodicals, Inc.