title: Application of Bayesian regression with singular value decomposition method in association studies for sequence data.
abstract: 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.
authors.affiliation: Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Xiuqing.Guo@cshs.org.
authors.forename: Soonil
authors.initials: S
authors.lastname: Kwon
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yan
authors.forename: Jinrui
authors.initials: J
authors.lastname: Cui
authors.forename: Jie
authors.initials: J
authors.lastname: Yao
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.forename: Donald
authors.initials: D
authors.lastname: Tsiang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo