Polygenic risk scores: An overview from bench to bedside for personalised medicine

Abstract

Since the first polygenic risk score (PRS) in 2007, research in this area has progressed significantly. The increasing number of SNPs that have been identified by large scale GWAS analyses has fuelled the development of a myriad of PRSs for a wide variety of diseases and, more recently, to PRSs that potentially identify differential response to specific drugs. PRSs constitute a composite genomic biomarker and potential applications for PRSs in clinical practice encompass risk prediction and disease screening, early diagnosis, prognostication, and drug stratification to improve efficacy or reduce adverse drug reactions. Nevertheless, to our knowledge, no PRSs have yet been adopted into routine clinical practice. Beyond the technical considerations of PRS development, the major challenges that face PRSs include demonstrating clinical utility and circumnavigating the implementation of novel genomic technologies at scale into stretched healthcare systems. In this review, we discuss progress in developing disease susceptibility PRSs across multiple medical specialties, development of pharmacogenomic PRSs, and future directions for the field.

Keywords: cancer; cardiovascule disease; genetic risk score; metabolic disease; neuropsychiatric disorders; personalised medicine; pharmacogenomics; polygenic risk score.

FIGURE 1

Common features of PRSs and the ideal individualised areas an optimal PRS identifies to produce a personalised medicine approach to future healthcare.

FIGURE 2

A diagram demonstrating positive and negative factors influencing PRS development and the potential clinical utility of PRSs from birth to death. The strengths of the current studies are highlighted in green at the top of the figure, while limitations are shown in red. The bottom half of the figure provides the potential timepoints for utilization of PRSs through the life cycle from birth to death.