在神经性厌食症的途径水平上的多基因性.
Jiayi Xu1, Jessica S Johnson2, Chaoyu Liu1,3
1Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
medRxiv : the preprint server for health sciences
|November 24, 2025
概括
在途径层面的多基因风险得分揭示了神经性厌食症 (AN) 的遗传结构. 路径聚合,特别是在大脑和新陈代谢中,显著增加了AN风险,改善了疾病预测.
科学领域:
- 遗传学 是一个遗传学.
- 精神病学是一个精神病学.
- 计算生物学 计算生物学
背景情况:
- 全基因组关联研究 (GWAS) 揭示了常见疾病的多基因架构.
- 在神经性厌食症 (AN) 等复杂疾病中,跨生物通路的遗传风险的聚合仍然不太了解.
研究的目的:
- 在神经性厌食症 (AN) 的途径水平上研究多基因性.
- 开发基于路径的多基因风险得分 (路径PRS) 用于在AN中建模遗传风险.
- 探索路径聚合如何影响AN风险和预测.
主要方法:
- 基于路径构建的多基因风险得分 (路径PRS) 为3,687个AN病例和11,257个对照.
- 使用邦费罗尼校正确定了与AN相关的途径.
- 分析了路径PRS,AN病例比例和整体遗传风险之间的相关性.
主要成果:
- 在大脑,新陈代谢,免疫力和发育方面确定了497条与AN相关的途径.
- 观察到排名最高的途径数量与AN风险之间存在强烈的正相关性 (r=0.74).
- 功能内部和功能间的途径聚合 (例如,大脑-大脑,大脑-新陈代谢) 显著增加了AN风险.
- 途径PRS表现出比全基因组PRS更高的AN预测能力.
结论:
- 多遗传性在通路层面上运作,有助于AN的复杂遗传责任.
- 途径级分析为疾病机制提供了新的见解,并为AN提供了预测.
- 确定了与增加AN风险相关的特定途径组合,表明了潜在的治疗点.
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