Implementation of Individualised Polygenic Risk Score Analysis: A Test Case of a Family of Four

Abstract

AbstractPolygenic risk scores (PRS) have been widely applied in research studies, showing how population groups can be stratified into risk categories for many common conditions. As healthcare systems consider applying PRS to keep their populations healthy, little work has been carried out demonstrating their implementation at an individual level. We performed a systematic curation of PRS sources from established data repositories, selecting 27 phenotypes, comprising almost 40 million SNPs related to cancer, cardiovascular, metabolic and autoimmune diseases. We tested selected phenotypes using whole genome sequencing data for a family of four family related individuals, with the 1000 Genomes Project (1000G) Phase III participants as background populations. Over 98 billion allele effects were calculated in order to obtain the PRS for each of the individuals analysed here. PRS calculation for the 1000G cohort of 2,504 participants allows us to develop a methodology for risk inference and general PRS deployment. Our approach for PRS implementation advances the discussion on the adoption of PRS in a preventative healthcare setting.