Cross-Ancestry Genetic Risk Scores for Predicting Antipsychotic Response

Schizophrenia (SCZ) is a debilitating mental illness treated with antipsychotics (APs), but treatment is often inefficient and guided by trial-and-error. Personalized AP prescription based on genetics may improve treatment response. AP response is affected by hundreds of genetic variants which each have a small effect, and polygenic risk scores (PRS), which combine these effects, have been associated with response. Ancestry is a key factor in PRS, but studies of PRS for AP response have largely been conducted in European populations, which is not generalizable to other ancestries. To address this gap, we will study AP response in the ancestrally diverse ‘All of Us’ (AoU) cohort. We will compare standard single-ancestry PRSs to advanced multi-ancestry PRSs, to assess which is better at predicting AP response across populations. Findings will advance our understanding of how the genetics of AP response varies across ancestries, and guide strategies on accounting for this for the equitable development of personalized medicine tools. By collaborating with Dr. Lewis, I will learn advanced techniques to study genetics across ancestries, and her lab will benefit by gaining experience with the diverse AoU dataset. This will strengthen past collaborations between the two labs, and open new avenues of shared discovery.

Faculty Supervisor:

James L Kennedy

Student:

Partner:

King's College London

Discipline:

Life Sciences

Sector:

Education

University:

University of Toronto

Program: