基因组平台特定的多基因风险评分对乳腺癌风险分层的影响
Peh Joo Ho1,2, Alexis Jiaying Khng1, Joanna Hui Juan Tan1
1Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
Communications medicine
|December 12, 2025
概括
基因组平台的选择显著影响乳腺癌的多基因风险评分 (PRS),可能会改变个体风险分类. 标准化PRS平台对于一致的临床实施和准确的风险分层至关重要.
科学领域:
- 基因组学就是基因组学.
- 生物信息学是一种生物信息学.
- 临床遗传学 临床遗传学
背景情况:
- 对于临床多基因风险评分 (PRS) 实施中的基因定型平台,还没有确立的标准.
- 之前的研究平均基因组性能,忽视了平台特定对PRS准确性的影响.
- 对跨平台的313种乳腺癌PRS (PRS313) 的评估对于风险分层至关重要.
研究的目的:
- 为了比较PRS313在各种基因型阵列和低覆盖全基因组测序中的性能.
- 评估平台可变性对高风险分类的影响.
- 确定不同基因组平台之间的一致性和协议,用于PRS计算.
主要方法:
- 比较了来自全球选阵列 (GSA),OncoArray-500K,全球多样性阵列 (GDA) 和定制的Axiom阵列与低覆盖全基因组测序 (lc-WGS) 的 PRS313.
- 使用卡帕统计数据评估高风险分类的一致性 (PRS313 > 0.6).
- 利用线性模型来预测平台之间的PRS313和分析平均校正前后的协议.
主要成果:
- 与桑格序列的英德尔对应在各个平台上有很大的差异 (卡帕:0.007-1.000).
- 具有高归算重叠的数组,如GDA和GSA,显示出更大的一致性 (斜率=0.986).
- 经过平均校正后,高风险分类协议得到了改善 (Kappa=0.650对比0.552),但仍然存在很大的差异,在所有平台上,在92人中只有7人被一致归类为高风险.
结论:
- 基因型和测序中的平台特定变异性可以显著影响PRS估计.
- 这些变化可能导致个人在临床相关风险值附近重新分类.
- 基因组平台的标准化对于可靠的临床PRS实施是必要的.
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