基于多基因风险评分来预测抗精神病药物的疗效:一个真实世界的队列研究
Marco De Pieri1,2,3,4, Marco Ferrari1, Giorgio Pistis5
1Center for Research in Medical Pharmacology, Varese, Italy.
Frontiers in pharmacology
|March 25, 2024
概括
对抗精神病反应的多基因风险评分 (PRS) 在真实世界患者数据中显示出显著的关联. 然而,它的预测准确性目前对于临床使用来说太低了.
科学领域:
- 精神病学是一个精神病学.
- 遗传学 遗传学 是一个
- 药物基因组学 药物基因组学
背景情况:
- 对抗精神病治疗的反应在个体之间有很大差异.
- 遗传因素,包括单核酸多态 (SNPs),影响这种变异性.
- 多基因风险评分 (PRS) 是多个遗传变异的综合影响.
研究的目的:
- 调查PRS对抗精神病反应 (PRS_response) 和不同患者队列中的治疗结果之间的关联.
- 评估PRS_response在现实世界临床环境中的预测效用.
- 评估精神分裂症风险PRS与抗精神病治疗反应的关联.
主要方法:
- 使用在全基因组关联研究 (GWAS) 中识别的SNP构建了一个PRS_response.
- 在460名患有各种精神病诊断的患者的真实实验样本中,测试了PRS_response与抗精神病治疗反应的关联.
- 还分析了另外两个针对精神分裂症风险的PRS.
主要成果:
- 在整体队列和子组中,PRS_response与抗精神病反应有显著的关联,包括精神分裂症谱系和双相情感障碍患者.
- 在精神分裂症患者中,PRS_response显示出显著的关联 (OR = 1.27,p = 0.01).
- 灵敏度和特异性分析表明预测性能不足于最佳,不允许临床应用.
结论:
- 来自GWAS的PRS_response与现实世界队列中的抗精神病治疗反应有显著的关联.
- 尽管具有统计学意义,但目前的PRS_response缺乏足够的预测准确性,无法在临床实施.
- 需要进一步的研究来完善PRS模型来预测抗精神病反应.
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