Comparative analysis of genomic methods for identifying genetic variants in actionable pharmacogenes

This research project aims to advance personalized medicine by understanding how genetic variation influences drug response, with the goal of improving both the safety and efficacy of pharmacotherapy. Pharmacogenetics focuses on tailoring drug selection and dosage to each patient’s unique genetic profile, moving beyond the “average patient” approach used in traditional medicine.

Our team analyzed genome-wide data from 1,533 participants in the CHUV Genomic Biobank (BGC) and 4,791 participants in the population-based CoLaus|PsyCoLaus study. We found that 97% of participants carried at least one clinically actionable pharmacogenetic variant. Notably, 31% of hospital patients were prescribed at least one medication for which they carried a high-risk variant, highlighting the need to adjust drug type or dosage according to international pharmacogenetic guidelines. These findings demonstrate the broad potential for genetically informed prescribing to reduce adverse drug reactions (ADRs) and optimize treatment outcomes.

Building on these results, we are conducting a retrospective study of 500 BGC patients with documented ADRs to evaluate whether low-pass whole-genome sequencing (LP-WGS) can outperform conventional genotyping arrays in clinical pharmacogenetics. By integrating genomic data with patients’ medication histories and ADR records, we aim to determine which assay provides the most reliable variant detection and coverage for pharmacogenes. The study also seeks to estimate how many ADRs could have been prevented had these methods been applied proactively, supporting the development of standardized, genome-based protocols to enhance drug safety in routine healthcare.

Performed in collaboration with Prof. François Girardin, Head of the CHUV Service of Pharmacology, and supported by the UNIL Faculty of Biology and Medicine, this research underscores the need to integrate pharmacogenetic testing into clinical practice, moving Switzerland closer to truly precision-guided pharmacotherapy.