多基因风险评分提高了对眼睛高血压治疗研究中的初级开放角度视光眼的预测
Rishabh K Singh1,2, Yan Zhao3, Tobias Elze2
1Department of Ophthalmology, Columbia University Medical Center, New York, NY.
medRxiv : the preprint server for health sciences
|August 30, 2023
概括
多基因风险评分 (PRS) 识别了患初级开角青光眼 (POAG) 风险较高的个体,并预测了眼睛高血压患者的早期疾病发作. 早期治疗可能会减轻遗传风险,延迟POAG诊断.
科学领域:
- 眼科医生 眼科 眼科
- 遗传学 是一个遗传学.
- 生物统计学 生物统计学
背景情况:
- 主要开角玻璃眼 (POAG) 是视力丧失的重要原因,其特点是具有高遗传性和众多已识别的遗传风险位点.
- 多基因风险评分 (PRS) 量化了个体对POAG.com等复杂疾病的总体遗传倾向.
- 评估PRS在眼睛高血压患者中分层风险的实用性对于早期干预至关重要.
研究的目的:
- 评估PRS是否增强了被诊断患有眼睛高血压的患者初级开角青光眼 (POAG) 的风险分层.
- 确定PRS是否可以预测POAG在这个患者队列中的发病时间和诊断年龄.
主要方法:
- 对来自眼睛高血压治疗研究 (OHTS) 的数据进行了后期分析,涉及1009名参与者.
- 多基因风险得分 (PRS) 计算使用大规模的跨祖先POAG元分析总结统计数据和英国生物库数据.
- 包括Cox比例危险模型在内的生存回归分析被用来评估PRS和POAG发展之间的关联,比较具有和没有PRS的预测模型性能.
主要成果:
- 开发POAG的参与者与没有开发POAG的参与者相比,平均PRS显著更高 (p < 0.01).
- 每增加PRS分位数都与1.36%的POAG风险上升有关,转换率在分位数之间从9.5%到21.8%不等.
- 与基线OHTS模型 (C指数=0.75) 相比,将PRS纳入预测模型显著提高了预测准确性 (C指数=0.77).
结论:
- 升高的PRS与眼睛高血压患者的POAG风险增加和早期发病有关.
- 早期的治疗干预可以抵消与高遗传负担相关的高风险,可能会将POAG诊断推迟多达5.2年.
- 将PRS整合到临床评估中提供了一个有价值的工具,可以改善在风险人群中预测POAG发病的预测.
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