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Application of Bayesian regression with singular value decomposition method in association studies for sequence data

机译:贝叶斯回归奇异值分解方法在序列数据关联研究中的应用

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摘要

Genetic association studies usually involve a large number of single-nucleotide polymorphisms (SNPs) (k) and a relative small sample size (n), which produces the situation that k is much greater than n. Because conventional statistical approaches are unable to deal with multiple SNPs simultaneously when k is much greater than n, single-SNP association studies have been used to identify genes involved in a disease’s pathophysiology, which causes a multiple testing problem. To evaluate the contribution of multiple SNPs simultaneously to disease traits when k is much greater than n, we developed the Bayesian regression with singular value decomposition (BRSVD) method. The method reduces the dimension of the design matrix from k to n by applying singular value decomposition to the design matrix. We evaluated the model using a Markov chain Monte Carlo simulation with Gibbs sampler constructed from the posterior densities driven by conjugate prior densities. Permutation was incorporated to generate empirical p-values. We applied the BRSVD method to the sequence data provided by Genetic Analysis Workshop 17 and found that the BRSVD method is a practical method that can be used to analyze sequence data in comparison to the single-SNP association test and the penalized regression method.
机译:遗传关联研究通常涉及大量单核苷酸多态性(SNP)(k)和相对较小的样本量(n),这会导致k远大于n的情况。由于传统的统计方法无法在k大于n时同时处理多个SNP,因此单SNP关联研究已被用于识别与疾病的病理生理学有关的基因,这会导致多重检测问题。为了评估k远大于n时多个SNP同时对疾病性状的贡献,我们开发了具有奇异值分解(BRSVD)方法的贝叶斯回归。该方法通过将奇异值分解应用于设计矩阵,将设计矩阵的维数从k减少到n。我们使用马氏链蒙特卡洛模拟和Gibbs采样器评估了模型,该采样器由共轭先验密度驱动的后验密度构造而成。合并排列以生成经验p值。我们将BRSVD方法应用于遗传分析研讨会17提供的序列数据,发现BRSVD方法是一种实用的方法,与单SNP关联检验和惩罚回归方法相比,可用于分析序列数据。

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