arXiv subjects

Xihong Lin

Publications and source records attributed to Xihong Lin.

22 records · Page 2Linked to original sources

arXiv2017

Set-Based Tests for Genetic Association Using the Generalized Berk-Jones Statistic

Studying the effects of groups of Single Nucleotide Polymorphisms (SNPs), as in a gene, genetic pathway, or network, can provide novel insight into complex diseases, above that which can be gleaned from studying SNPs individually. Common challenges in set-based genetic association testing include weak effect sizes, correlation between SNPs in a SNP-set, and scarcity of signals, with single-SNP effects often ranging from extremely sparse to moderately sparse in number. Motivated by these challenges, we propose the Generalized Berk-Jones (GBJ) test for the association between a SNP-set and outcome. The GBJ extends the Berk-Jones (BJ) statistic by accounting for correlation among SNPs, and it provides advantages over the Generalized Higher Criticism (GHC) test when signals in a SNP-set are moderately sparse. We also provide an analytic p-value calculation procedure for SNP-sets of any finite size. Using this p-value calculation, we illustrate that the rejection region for GBJ can be described as a compromise of those for BJ and GHC. We develop an omnibus statistic as well, and we show that this omnibus test is robust to the degree of signal sparsity. An additional advantage of our method is the ability to conduct inference using individual SNP summary statistics from a genome-wide association study. We evaluate the finite sample performance of the GBJ though simulation studies and application to gene-level association analysis of breast cancer risk.

stat.AP↗

arXiv2015

Hypothesis testing for high-dimensional sparse binary regression

In this paper, we study the detection boundary for minimax hypothesis testing in the context of high-dimensional, sparse binary regression models. Motivated by genetic sequencing association studies for rare variant effects, we investigate the complexity of the hypothesis testing problem when the design matrix is sparse. We observe a new phenomenon in the behavior of detection boundary which does not occur in the case of Gaussian linear regression. We derive the detection boundary as a function of two components: a design matrix sparsity index and signal strength, each of which is a function of the sparsity of the alternative. For any alternative, if the design matrix sparsity index is too high, any test is asymptotically powerless irrespective of the magnitude of signal strength. For binary design matrices with the sparsity index that is not too high, our results are parallel to those in the Gaussian case. In this context, we derive detection boundaries for both dense and sparse regimes. For the dense regime, we show that the generalized likelihood ratio is rate optimal; for the sparse regime, we propose an extended Higher Criticism Test and show it is rate optimal and sharp. We illustrate the finite sample properties of the theoretical results using simulation studies.

math.ST↗

arXiv2014

Joint analysis of SNP and gene expression data in genetic association studies of complex diseases

Genetic association studies have been a popular approach for assessing the association between common Single Nucleotide Polymorphisms (SNPs) and complex diseases. However, other genomic data involved in the mechanism from SNPs to disease, for example, gene expressions, are usually neglected in these association studies. In this paper, we propose to exploit gene expression information to more powerfully test the association between SNPs and diseases by jointly modeling the relations among SNPs, gene expressions and diseases. We propose a variance component test for the total effect of SNPs and a gene expression on disease risk. We cast the test within the causal mediation analysis framework with the gene expression as a potential mediator. For eQTL SNPs, the use of gene expression information can enhance power to test for the total effect of a SNP-set, which is the combined direct and indirect effects of the SNPs mediated through the gene expression, on disease risk. We show that the test statistic under the null hypothesis follows a mixture of $χ^2$ distributions, which can be evaluated analytically or empirically using the resampling-based perturbation method. We construct tests for each of three disease models that are determined by SNPs only, SNPs and gene expression, or include also their interactions. As the true disease model is unknown in practice, we further propose an omnibus test to accommodate different underlying disease models. We evaluate the finite sample performance of the proposed methods using simulation studies, and show that our proposed test performs well and the omnibus test can almost reach the optimal power where the disease model is known and correctly specified. We apply our method to reanalyze the overall effect of the SNP-set and expression of the ORMDL3 gene on the risk of asthma.

stat.AP↗

arXiv2012

Parallelism, Uniqueness, and Large-Sample Asymptotics for the Dantzig Selector

The Dantzig selector (Candes and Tao, 2007) is a popular l1-regularization method for variable selection and estimation in linear regression. We present a very weak geometric condition on the observed predictors which is related to parallelism and, when satisfied, ensures the uniqueness of Dantzig selector estimators. The condition holds with probability 1, if the predictors are drawn from a continuous distribution. We discuss the necessity of this condition for uniqueness and also provide a closely related condition which ensures uniqueness of lasso estimators (Tibshirani, 1996). Large sample asymptotics for the Dantzig selector, i.e. almost sure convergence and the asymptotic distribution, follow directly from our uniqueness results and a continuity argument. The limiting distribution of the Dantzig selector is generally non-normal. Though our asymptotic results require that the number of predictors is fixed (similar to (Knight and Fu, 2000)), our uniqueness results are valid for an arbitrary number of predictors and observations.

math.ST↗