对超越跨诊断性遗传风险的精神疾病多基因评分的特异性
Engin Keser1, Wangjingyi Liao2, Andrea G Allegrini3
1Social, Genetic and Developmental Psychiatry Centre, King's College London, London, United Kingdom.
JAMA network open
|January 8, 2026
概括
精神疾病的多基因分数 (PGS) 主要是由共同的遗传责任驱动的,而不是特定的特征. 考虑到这一跨诊断因素,可以提高PGS的特异性,并为一般精神病理学风险分层提供信息.
科学领域:
- 精神病学和遗传学 精神病学和遗传学
- 行为科学 行为科学
背景情况:
- 多基因分数 (PGS) 估计了精神疾病的遗传责任.
- 目前PGS的有限疾病特异性阻碍了临床和研究应用.
研究的目的:
- 确定精神病PGS特征关联是否源于跨诊断或疾病特异性遗传责任.
- 调查跨诊断 (p) 和疾病特异性 (非p) PGSs的实用性.
主要方法:
- 利用基于人口的队列 (双胞胎早期发育研究) 的6567名25-28岁的参与者.
- 评估了定量症状得分和自我报告的精神病诊断.
- 未经纠正的PGS,一个跨诊断的PGS (p) 和残留疾病特定的PGS (非p) 的比较协会.
主要成果:
- 经过诊断的PGS (p) 与大多数症状结局的相关性比未经纠正的PGS相比具有相似或更强的相关性.
- 未经纠正的PGS中的大部分遗传信号与跨诊断责任有关,在考虑p时显著减弱.
- 一些疾病特异性 (非p) PGS保留了显著的关联,表明对PTSD和神经性厌食症等疾病的残留特异性.
结论:
- 精神病PGS与结果的关联主要是由跨诊断遗传责任驱动的.
- 考虑共享的遗传影响可以增强PGS的特异性.
- 跨诊断分数为风险分层和针对一般精神病理的干预提供了潜力.
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