Volume 16, Issue 3

In this article, we consider variable selection for correlated high dimensional DNA methylation markers as multivariate outcomes. A novel weighted square-root LASSO procedure is proposed to estimate the regression coefficient matrix. A key feature of this method is tuning-insensitivity, which greatly simplifies the computation by obviating cross validation for penalty parameter selection. A precision matrix obtained via the constrained ℓ 1 minimization method is used to account for the within-subject correlation among multivariate outcomes. Oracle inequalities of the regularized estimators are derived. The performance of our proposed method is illustrated via extensive simulation studies. We apply our method to study the relation between smoking and high dimensional DNA methylation markers in the Normative Aging Study (NAS).

Multilocus haplotype analysis of candidate variants with genome wide association studies (GWAS) data may provide evidence of association with disease, even when the individual loci themselves do not. Unfortunately, when a large number of candidate variants are investigated, identifying risk haplotypes can be very difficult. To meet the challenge, a number of approaches have been put forward in recent years. However, most of them are not directly linked to the disease-penetrances of haplotypes and thus may not be efficient. To fill this gap, we propose a mixture model-based approach for detecting risk haplotypes. Under the mixture model, haplotypes are clustered directly according to their estimated disease penetrances. A theoretical justification of the above model is provided. Furthermore, we introduce a hypothesis test for haplotype inheritance patterns which underpin this model. The performance of the proposed approach is evaluated by simulations and real data analysis. The results show that the proposed approach outperforms an existing multiple testing method.

Many gene- and pathway-based association tests have been proposed in the literature. Among them, the SKAT is widely used, especially for rare variants association studies. In this paper, we investigate the connection between SKAT and a principal component analysis. This investigation leads to a procedure that encompasses SKAT as a special case. Through simulation studies and real data applications, we compare the proposed method with some existing tests.

Linear principal component analysis (PCA) is a widely used approach to reduce the dimension of gene or miRNA expression data sets. This method relies on the linearity assumption, which often fails to capture the patterns and relationships inherent in the data. Thus, a nonlinear approach such as kernel PCA might be optimal. We develop a copula-based simulation algorithm that takes into account the degree of dependence and nonlinearity observed in these data sets. Using this algorithm, we conduct an extensive simulation to compare the performance of linear and kernel principal component analysis methods towards data integration and death classification. We also compare these methods using a real data set with gene and miRNA expression of lung cancer patients. First few kernel principal components show poor performance compared to the linear principal components in this occasion. Reducing dimensions using linear PCA and a logistic regression model for classification seems to be adequate for this purpose. Integrating information from multiple data sets using either of these two approaches leads to an improved classification accuracy for the outcome.