We propose in the renewal of this MERIT award application to continue developing advanced statistical and
computational methods for analysis of correlated and high-dimensional data, which arise frequently in health
science research, especially in cancer research. Correlated data are often observed in observational
studies and clinical trials, such as longitudinal studies and familial studies. High-dimensional data have
emerged rapidly in recent years due to the advance of high-throughput 'omics technologies, e.g, in Genome-
Wide Association Studies (GWAS), and genome-wide epigenetic (DNA methylation) studies. Massive next
generation sequencing data are soon available. There is an urgent need to develop advanced stati stical and
computational methods for analyzing such high throughput 'omics data in observational studies and clinical
trials. We propose to develop statistical and computational methods for analysis of (1) genome-wide
association studies; (2) sequencing data for studying rare variant effects; (3) genome-wide DNA methylation
studies; (4) gene-gene and gene-environment interactions. We will develop methods for both case-control
studies and cohort studies, such as longitudinal studies and survival studies. We will study the theoretical
properties of the proposed methods and evaluate the finite s ample performance using simulation studies.
We will develop efficient numerical algorithms and user-friendly statistical software, and disseminate these
tools to health sciences researchers. In collaboration with biomedical investigators, we will apply the
proposed models methods to data from several genome-wide epidemiological studies in cancer and other
chronic diseases.
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