Nilanjan Chatterjee, PhD
Bloomberg Distinguished Professor
Department of Biostatistics, Bloomberg School of Public Health, Department of Oncology, School of Medicine Johns Hopkins University
Polygenic Risk Score: Development, Validation and Application
While polygenic risk scores (PRS) for various complex traits are now rapidly emerging from large genome-wide association studies, there remains substantial methodological issues for moving them closer to clinical applications. In this talk, I will provide an overview of recent methodological developments and challenges faced in building, validating and applying PRS. To begin with, I will describe sample size requirements for future GWAS for building improved PRS based on recent analyses of genetic architecture of complex traits. I will then review simple and complex machine leaning methods for building PRS, and challenges in their applications to multi-ethnic populations. Further, I will describe framework for building and evaluating PRS in the presence of other risk factors and, will discuss relevant metrices for evaluating clinical utility of PRS using absolute risk models and existing clinical guidelines. Examples will be drawn from recent studies of cancers and heart diseases.
