对13种主要精神疾病进行转录组范围的结构方程建模,用于跨障碍风险和药物重定位
Andrew D Grotzinger1,2, Kritika Singh3,4, Tyne W Miller-Fleming3,4
1Institute for Behavioral Genetics, University of Colorado Boulder, Boulder.
JAMA psychiatry
|June 14, 2023
概括
这项研究确定了与13种精神疾病中共同和独特风险相关的基因表达模式. 这些发现可能会指导复杂的心理健康状况的药物发现.
科学领域:
- 基因组学就是基因组学.
- 精神病学研究 精神病学研究
- 药理学 药理学是指药理学的学科.
背景情况:
- 精神疾病表现出显著的并发症和遗传重叠.
- 多变量方法对于理解复杂的精神病风险路径至关重要.
- 识别基因表达模式可以促进药物发现和用于多药学的重新利用.
研究的目的:
- 识别与精神疾病之间的遗传融合和分歧相关的基因表达模式.
- 找到针对这些基因的现有药理干预措施,用于药物重新定位.
主要方法:
- 应用了一种多变量转录组方法,即转录组全方位结构方程建模 (T-SEM).
- 研究了与13种精神疾病中的5种基因组因素相关的基因表达模式.
- 利用公共数据库来识别潜在的药物重用候选人.
主要成果:
- T-SEM确定了466个与基因组因素相关的基因和36个具有疾病特异性影响的基因.
- 发现最强的关联是思维障碍因素 (双相情感障碍,精神分裂症).
- 一些现有的药物被确定为重定向以准关键基因.
结论:
- 这项研究揭示了精神疾病背后的基因表达模式的重叠和独特性.
- 开发的框架为共患精神疾病的新药学干预提供了潜力.
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