反应的途径特异性多基因评分用于预测双极性障碍患者的临床治疗反应
medRxiv : the preprint server for health sciences
|April 8, 2025
概括
路径特定的多基因分数 (PSPGS) 提高了对双相情感障碍中反应的预测. 这些得分提供了比传统的全基因组得分更好的生物学见解,用于精神病治疗选择.
科学领域:
- 精神病学遗传学 精神病学遗传学
- 药物基因组学 药物基因组学
- 双极性障碍研究研究
背景情况:
- 多基因分数 (PGS) 显示出预测精神病治疗反应的前景,但缺乏明确的生物解释.
- 调查底层反应的生物学途径对于双相情感障碍的个性化医学至关重要.
研究的目的:
- 开发和验证特定途径的多基因分数 (PS PGS) 用于预测双相情感障碍 (BD) 中的反应.
- 与传统的PGS相比,评估PS PGS的生物解释性和预测性能.
主要方法:
- 使用受影响路径的基因开发了9个PSPGS.
- 在国际遗传学联盟 (N=2367) 中评估了PS与反应的PGS关联,并在PsyCourse/BipoLife队列 (N=207) 中得到验证.
- 使用逻辑和线性回归,对共变量进行调整,并应用多重测试校正.
主要成果:
- 与PSPGS相关的反应对乙胆,GABA,通道信号,线粒体,昼夜节律和GSK通路 (R2 0.29%-1.91%).
- 结合PS解释了3.71%的变异;GABA和CIR协会被复制.
- 最高的乙胆PS PGS分位数显示,良好的反应的可能性是3.03倍.
结论:
- PS PGS 提供与全基因组 PGS 的可比性预测性能,具有增强的生物解释性.
- PS PGS 使用较少的遗传变异,促进对反应机制的特定途径调查.
- 这种方法有助于理解反应的遗传基础,并优化双相情感障碍的治疗选择.
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