Cohort: Pharmacogenetics

This sequencing project will enable improvements to drug safety and effectiveness for children by making genomic data on their responses and adverse reactions to various medications more widely accessible to researchers and health regulatory agencies.

Abstract: This project will leverage the existing resources of the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) to bring a pediatric component to the Pan Canadian Genome Library and allow CPNDS to continue its work in making medications safer for children locally, nationally and internationally. Over the past 20 years, the CPNDS has collected DNA and biological samples from over 12,350 patients together with comprehensive demographic and clinical data that characterize their responses to over 100,000 medication uses and over 10,000 severe adverse drug reactions. This number is remarkable given that pediatric diseases like cancers are rare and severe adverse drug reactions are rare occurrences as well. Some patients have more than 40 years of longitudinal data. These patients were recruited and enrolled from 14 academic health centres in geographically diverse locations across eight provinces in Canada (British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia and Newfoundland). This funding is critical for the continuation of this network.

This project has four primary objectives to support the Pan-Canadian Genomics Library (PCGL):

1. Contact previously recruited patients in the CPNDS databank and re-consent them for inclusion of their de-identified clinical and genomic data into the Pan-Canadian Genomics Library (PCGL) (n=6,985). [Activities 1 & 2]
2. Continue to prospectively recruit and enroll patients at our 10 existing study sites over the course of this four-year project (n=4,000). This additional recruitment will be conducted through the lens of significantly enhancing inclusion, diversity, equity and accessibility (IDEA) of the cohort. These samples are being added to ensure that future research beyond this project has a richer and more diverse database of clinical and genomic data to work with. [Activities 1 & 2]
3. Improve the genomic data holdings from genome-wide genotype typing data (GWAS) to whole-genome sequencing data – short-read sequencing will be conducted for n=10,985 and long-read sequencing will be conducted for n=1,000. [Activities 3, 4 and 5] This will allow for much more in-depth investigations of drug-induced harm.
4. Conduct genomic analyses using the generated whole-genome sequencing data to explore and identify biomarkers that are predictive of drug-induced harm associated with seven severe adverse drug reactions experienced by pediatric oncology patients in Canada [Activity 6] while facilitating dialogue and engaging with the multidisciplinary team assembled for this project [Activity 7]. The generation of this data will facilitate research and innovation to improve drug safety and effectiveness in children by making these data more widely accessible to researchers from academic, charitable organizations, health centres, for-profit private companies and health regulatory agencies.