arXiv:2504.00024stat.MEcs.AI2025-04被引 1

提出多位点风险预测曲线,提升复杂疾病遗传风险评估准确性。

A multi-locus predictiveness curve and its summary assessment for genetic risk prediction

  • 基于非参数方法构建多基因位点预测曲线,适用于病例对照研究。
  • 全局与局部预测U统计量分别衡量整体和特定人群的预测效果,优于传统指标。
  • 在罕见变异模型中局部预测U表现更优,适合临床关注人群分析。

随着高通量基因分型和测序技术的发展,全面评估大量遗传标记在疾病预测中的作用成为可能。然而,现有方法难以有效衡量多个遗传变异的联合预测效果。本文提出多标记预测曲线,并为病例对照研究提供非参数构建方法;进一步引入全局预测U和局部预测U,分别总结全人群和临床关注亚群的预测能力。文章揭示了预测曲线与ROC曲线、洛伦兹曲线的关联性。通过模拟对比发现,预测U在无偏性和稳健性方面优于R²、总收益和平均熵;在罕见变异疾病模型中,局部预测U表现更优。最后,基于尼古丁依赖风险模型的真实数据验证了该方法的有效性。

原文摘要 · Abstract (English)

With the advance of high-throughput genotyping and sequencing technologies, it becomes feasible to comprehensive evaluate the role of massive genetic predictors in disease prediction. There exists, therefore, a critical need for developing appropriate statistical measurements to access the combined effects of these genetic variants in disease prediction. Predictiveness curve is commonly used as a graphical tool to measure the predictive ability of a risk prediction model on a single continuous biomarker. Yet, for most complex diseases, risk prediciton models are formed on multiple genetic variants. We therefore propose a multi-marker predictiveness curve and provide a non-parametric method to construct the curve for case-control studies. We further introduce a global predictiveness U and a partial predictiveness U to summarize prediction curve across the whole population and sub-population of clinical interest, respectively. We also demonstrate the connections of predictiveness curve with ROC curve and Lorenz curve. Through simulation, we compared the performance of the predictiveness U to other three summary indices: R square, Total Gain, and Average Entropy, and showed that Predictiveness U outperformed the other three indexes in terms of unbiasedness and robustness. Moreover, we simulated a series of rare-variants disease model, found partial predictiveness U performed better than global predictiveness U. Finally, we conducted a real data analysis, using predictiveness curve and predictiveness U to evaluate a risk prediction model for Nicotine Dependence.

遗传预测风险评估统计方法多基因评分

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