GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia.
GeneAnalytics Pathway Analysis and Genetic Overlap among Autism Spectrum Disorder, Bipolar Disorder and Schizophrenia.
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DOI：
10.3390/ijms18030527
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发表时间：
2017-02-28
影响因子：
5.6
通讯作者：
Manzardo AM
中科院分区：
文献类型：
--
作者：
Khanzada NS;Butler MG;Manzardo AM
双相情感障碍（BPD）和精神分裂症（SCH）表现出类似的神经精神行为障碍，包括社交互动和沟通障碍，在自闭症谱系障碍（ASD）中可以看到，多重重叠的遗传和环境影响涉及疾病的风险和病程。使用GeneAnalytics软件进行通路分析和遗传谱分析，对ASD（792个基因）、BPD（290个基因）和SCH（560个基因）的公开列表中获得的常见易感基因进行表征。等级评分是根据重叠基因的数量和性质、基因与疾病的关联、组织特异性和细分类别（如疾病、组织或功能途径）的基因功能得出的。这三种疾病共有23个基因，并映射到9个生物超通路，包括昼夜节律干扰（10个基因，得分= 37.0）、安非他命成瘾（5个基因，得分= 24.2）和婴儿猝死综合征（6个基因，得分= 24.1）。脑组织包括延髓（11个基因，评分为2.1）、丘脑（10个基因，评分为2.0）和下丘脑（9个基因，评分为2.0），共有6个基因（BDNF、DRD2、CHRNA7、HTR2A、SLC6A3和TPH2）。重叠基因影响多巴胺和血清素稳态和信号转导通路，影响情绪、行为和身体活动水平。调控昼夜节律通路的趋同效应支持神经精神疾病与睡眠中断伴缺氧和中枢脑干功能障碍之间的核心病因学关系。
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 (BDNF, DRD2, CHRNA7, HTR2A, SLC6A3, and TPH2). 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.