Exploring the genetic basis of complex traits

2014-10-06This thesis aims to explore the genetic basis of complex traits. It addresses this problem in two parts. ❧ The first part stems from the general difficulties encountered in previous efforts to explain complex traits with discovered associated genetic variants. Accordingly, increasing attention has been paid to rare variants that have been overlooked in traditional methods. To accommodate the special properties of rare variant studies, pooled sequencing is often used as a cost-effective design. Based on pooled sequencing data, we develop a unified approach for rare variants detection, allele frequency estimation and association studies. The method is thoroughly evaluated on both simulation data and a real re-sequencing dataset, and has shown superior performance. ❧ The second part further studies the problem of finding common genetic basis between traits. We propose a set of test statistics to detect genetic overlap between diseases, and a set of estimators to measure the size of genetic overlap. Performance of these methods under various scenarios is evaluated in simulation studies. Based on this, we choose the most appropriate method to study the relationship between diseases from the OMIM database and diseases in the catalog of GWAS. Both applications demonstrate the effectiveness of our methods in providing insights into the relationships among diseases based on their shared genetic mechanisms, and in identifying common genes underlying the genetic overlap between diseases