CLINICAL APPLICATIONS OF POLYGENIC SCORES: OPPORTUNITIES AND CHALLENGES

Polygenic scores (PGS) are arguably the best-substantiated biomarkers of risk available in psychiatry. In light of this, there is growing interest in their potential for informing clinical practice. However, prospects for the clinical translation of PGS face a number of formidable challenges including their limited predictive value, the Eurocentric bias of existing genomic data, ascertainment bias in training data, and the complex ethical, legal and social issues their use might raise. Beyond these, the complexities of real-world implementation have been under-explored. This presentation will review these issues, drawing on a variety of recent studies including the experience of the Electronic Medical Records and Genomics (eMERGE) Network which has been returning PGS in clinical practice for a range of common diseases across multiple U.S. health systems. We will also discuss the need for establishing performance metrics, factors bearing on the selection of viable use cases in psychiatry and the potential for enhancing risk prediction by integrating PGS with clinical risk models. The so-called “last mile” of translating prediction models into clinical practice is an arduous and complex process. An implementation science framework will be essential if the development and validation of PGS are to be more than an academic exercise.