多特征多基因概率风险评分增强了对祖先的玻璃眼预测
1Department of Ophthalmology and Visual Sciences, The Ohio State University, Columbus, OH 43210, USA.
medRxiv : the preprint server for health sciences
|April 8, 2025
概括
一个新的多基因概率风险评分 (PPRS) 通过整合多个特征和基因组数据,改善了初级开角青光眼 (POAG) 的预测. 这种方法增强了跨多元祖先的早期检测,有助于预防视力丧失.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 眼科医生 眼科 眼科
- 生物统计学 生物统计学
背景情况:
- 主要开角青光眼 (POAG) 是全球不可逆转失明的主要原因.
- 目前对POAG的风险评估工具缺乏足够的预测能力来进行早期检测.
- 早期发现POAG的有效策略对于预防视力丧失至关重要.
研究的目的:
- 开发和验证多特征多基因概率风险评分 (PPRS) 以提高POAG预测.
- 整合多个与眼相关的特征和功能性基因组注释,以提高预测准确度.
- 评估PPRS在不同祖先群体中的表现.
主要方法:
- 构建了POAG,眼内压 (IOP),垂直杯与圆盘比 (VCDR) 和视网膜神经纤维层 (RNFL) 厚度的多基因风险得分 (PRS),使用超过700万个变体和96个功能注释.
- 在PRS建设中采用SBayesRC方法.
- 在欧洲 (英国生物银行) 和拉丁美洲 (MAGGS) 队列中验证了多特征的PPRS.
主要成果:
- 多特征PPRS实现了优异的预测准确性,AUC值为0.814 (欧洲人) 和0.801 (拉丁裔),优于单特征模型 (AUC ≤0.79).
- 确定了祖先特异性的遗传贡献,IOP在欧洲人中最强,VCDR在拉丁裔中最强.
- 显示出显著的风险分层,最高的PPRS分位数与最低的分位数相比,显著增加POAG风险 (80.2倍于欧洲人,51.1倍于拉丁裔人).
结论:
- 整合多个与疾病相关的特征和功能注释显著提高了POAG.的多基因预测.
- 开发的PPRS提供了改善的风险分层和不同人群的病例捕获.
- 这种方法对有针对性的查,早期干预和减少POAG的全球负担有重大影响.
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