Hierarchical bayesian models for genome-wide association studies

Abstract

I consider a well-known problem in the field of statistical genetics called a genome-wide association study (GWAS) where the goal is to identify a set of genetic markers that are associated to a disease. A typical GWAS data set contains, for thousands of unrelated individuals, a set of hundreds of thousands of markers, a set of other covariates such as age, gender, smoking status and other risk factors, and a response variable that indicates the presence or absence of a particular disease. Due to biological phenomena such as the recombination of DNA and linkage disequilibrium, parents are more likely to pass parts of DNA that lie close to each other on a chromosome together to their offspring; this non-random association between adjacent markers leads to strong correlation between markers in GWAS data sets. As a statistician, I reduce the complex problem of GWAS to its essentials, i.e. variable selection on a large-p-small-n data set that exhibits multicollinearity, and develop solutions that complement and advance the current state-of-the-art methods. Before outlining and explaining my contributions to the field in detail, I present a literature review that summarizes the history of GWAS and the relevant tools and techniques that researchers have developed over the years for this problem.