A call for increased inclusivity and global representation in pharmacogenetic testing

April Kennedy; Gabriel Ma; Roozbeh Manshaei; Rebekah K Jobling; Raymond H Kim; Tamorah Lewis; Iris Cohn

doi:10.1038/s41525-024-00403-1

A call for increased inclusivity and global representation in pharmacogenetic testing

NPJ Genom Med. 2024 Feb 22;9(1):13. doi: 10.1038/s41525-024-00403-1.

Authors

April Kennedy^{1

2}, Gabriel Ma³, Roozbeh Manshaei⁴, Rebekah K Jobling^{4

5

6}, Raymond H Kim^{4

5

7}, Tamorah Lewis^{1

2

8}, Iris Cohn^{9

10

11}

Affiliations

¹ Division of Clinical Pharmacology and Toxicology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
² Program in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
³ University of Toronto, Toronto, ON, Canada.
⁴ Cardiac Genome Clinic, Ted Rogers Centre for Heart Research, The Hospital for Sick Children, Toronto, ON, Canada.
⁵ Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada.
⁶ Genome Diagnostics, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
⁷ Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁸ Division of Neonatology, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
⁹ Division of Clinical Pharmacology and Toxicology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. iris.cohn@sickkids.ca.
¹⁰ Program in Translational Medicine, The Hospital for Sick Children, Toronto, ON, Canada. iris.cohn@sickkids.ca.
¹¹ Cardiac Genome Clinic, Ted Rogers Centre for Heart Research, The Hospital for Sick Children, Toronto, ON, Canada. iris.cohn@sickkids.ca.

Abstract

Commercial pharmacogenetic testing panels capture a fraction of the genetic variation underlying medication metabolism and predisposition to adverse reactions. In this study we compared variation in six pharmacogenes detected by whole genome sequencing (WGS) to a targeted commercial panel in a cohort of 308 individuals with family history of pediatric heart disease. In 1% of the cohort, WGS identified rare variants that altered the interpretation of metabolizer status and would thus prevent potential errors in gene-based dosing.