Personalized Genetic Risk Profile: A New Tool to Guide Prevention of Serious Mental Illness

Serious mental illness (SMI) has devastating effects. The key clinical challenge is to identify individuals at increased risk for SMI for personalized prevention. However, the specialized clinical teams aiming to identify at-risk individuals face major challenges: risk assessment is suboptimal as only clinical characteristics are considered, and only psychosis is considered ignoring risk for SMI disorders without psychosis.Genetics has great potential to significantly improve identification of at-risk individuals. However, the major current problem preventing clinical implementation is that no appropriate method exists to accurately assess genetic risk of multiple SMI disorders. In this ambitious PersonalRiskProfile-project, my team and I will develop this much-needed method and software: the personalized genetic risk profile (PGRP)-method. PGRP will use advanced genetic techniques to simultaneously compute the risk for multiple SMI disorders that regularly but not always include psychosis: schizophrenia, bipolar disorder and major depressive disorder. Specifically, we aim to Optimize Prediction & Generalize to Diverse Ancestries (Aim 1), by including polygenic risk scores for SMI-disorders and auxiliary helper-traits, including rare genetic variants, and accounting for time-since-risk-assessment effects and family information; and to Validate & Prepare for Implementation (Aim 2), by validating PGRP in clinical cohorts, determining the best strategy to integrate PGRP with clinical risk assessment, investigating the stakeholders’ perspective, and developing an Online Dashboard to intuitively present PGRP-results. This ambitious interdisciplinary project provides a key step towards personalized prevention using genetics. I am uniquely qualified to lead, having established myself as international expert in statistical genetics through development of high-impact innovative methods and prestigious fellowships, combined with my clinical expertise as psychiatrist.