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自闭症谱系障碍、双相情感障碍和精神分裂症之间的基因分析通路分析及基因重叠

GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia.

作者信息

Khanzada Naveen S, Butler Merlin G, Manzardo Ann M

机构信息

Department of Psychiatry and Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA.

出版信息

Int J Mol Sci. 2017 Feb 28;18(3):527. doi: 10.3390/ijms18030527.

Abstract

Bipolar disorder (BPD) and schizophrenia (SCH) show similar neuropsychiatric behavioral disturbances, including impaired social interaction and communication, seen in autism spectrum disorder (ASD) with multiple overlapping genetic and environmental influences implicated in risk and course of illness. GeneAnalytics software was used for pathway analysis and genetic profiling to characterize common susceptibility genes obtained from published lists for ASD (792 genes), BPD (290 genes) and SCH (560 genes). Rank scores were derived from the number and nature of overlapping genes, gene-disease association, tissue specificity and gene functions subdivided into categories (e.g., diseases, tissues or functional pathways). Twenty-three genes were common to all three disorders and mapped to nine biological Superpathways including Circadian entrainment (10 genes, score = 37.0), Amphetamine addiction (five genes, score = 24.2), and Sudden infant death syndrome (six genes, score = 24.1). Brain tissues included the medulla oblongata (11 genes, score = 2.1), thalamus (10 genes, score = 2.0) and hypothalamus (nine genes, score = 2.0) with six common genes (, , , , , and ). Overlapping genes impacted dopamine and serotonin homeostasis and signal transduction pathways, impacting mood, behavior and physical activity level. Converging effects on pathways governing circadian rhythms support a core etiological relationship between neuropsychiatric illnesses and sleep disruption with hypoxia and central brain stem dysfunction.

摘要

双相情感障碍(BPD)和精神分裂症(SCH)表现出相似的神经精神行为障碍,包括社交互动和沟通受损,这在自闭症谱系障碍(ASD)中也有体现,且多种重叠的遗传和环境影响因素与疾病的风险和病程有关。使用基因分析软件进行通路分析和基因谱分析,以表征从已发表的ASD(792个基因)、BPD(290个基因)和SCH(560个基因)列表中获得的常见易感基因。排名分数来自重叠基因的数量和性质、基因与疾病的关联、组织特异性以及细分为各类别的基因功能(例如,疾病、组织或功能通路)。有23个基因在所有这三种疾病中都存在,并映射到九个生物学超级通路,包括昼夜节律同步(10个基因,分数=37.0)、苯丙胺成瘾(5个基因,分数=24.2)和婴儿猝死综合征(6个基因,分数=24.1)。脑组织包括延髓(11个基因,分数=2.1)、丘脑(10个基因,分数=2.0)和下丘脑(9个基因,分数=2.0),有6个共同基因(、、、、、和)。重叠基因影响多巴胺和5-羟色胺稳态以及信号转导通路,进而影响情绪、行为和身体活动水平。对昼夜节律调控通路的趋同作用支持了神经精神疾病与伴有缺氧和中枢脑干功能障碍的睡眠中断之间的核心病因学关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b63/5372543/2c4018396b96/ijms-18-00527-g001.jpg

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