Hai Yang, Wen Yalu
Department of Statistics, University of Auckland, Auckland 1010, New Zealand.
Bioinformatics. 2021 Apr 1;36(22-23):5415-5423. doi: 10.1093/bioinformatics/btaa1023.
Accurate disease risk prediction is essential for precision medicine. Existing models either assume that diseases are caused by groups of predictors with small-to-moderate effects or a few isolated predictors with large effects. Their performance can be sensitive to the underlying disease mechanisms, which are usually unknown in advance.
We developed a Bayesian linear mixed model (BLMM), where genetic effects were modelled using a hybrid of the sparsity regression and linear mixed model with multiple random effects. The parameters in BLMM were inferred through a computationally efficient variational Bayes algorithm. The proposed method can resemble the shape of the true effect size distributions, captures the predictive effects from both common and rare variants, and is robust against various disease models. Through extensive simulations and the application to a whole-genome sequencing dataset obtained from the Alzheimer's Disease Neuroimaging Initiatives, we have demonstrated that BLMM has better prediction performance than existing methods and can detect variables and/or genetic regions that are predictive.
The R-package is available at https://github.com/yhai943/BLMM.
Supplementary data are available at Bioinformatics online.
准确的疾病风险预测对于精准医学至关重要。现有模型要么假定疾病是由具有小到中等效应的预测因子组引起的,要么是由少数具有大效应的孤立预测因子引起的。它们的性能可能对潜在的疾病机制敏感,而这些机制通常事先并不清楚。
我们开发了一种贝叶斯线性混合模型(BLMM),其中使用稀疏回归和具有多个随机效应的线性混合模型的混合方法对遗传效应进行建模。通过计算效率高的变分贝叶斯算法推断BLMM中的参数。所提出的方法可以类似于真实效应大小分布的形状,捕获常见和罕见变异的预测效应,并且对各种疾病模型具有鲁棒性。通过广泛的模拟以及对从阿尔茨海默病神经影像倡议获得的全基因组测序数据集的应用,我们证明了BLMM比现有方法具有更好的预测性能,并且可以检测具有预测性的变量和/或遗传区域。
R包可在https://github.com/yhai943/BLMM获取。
补充数据可在《生物信息学》在线获取。