Should secondary pharmacogenomic variants be actively screened and reported when diagnostic genome-wide sequencing is
Jan M Friedman1, Yvonne Bombard2, Bruce Carleton3
1Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Insights
This paper reviews ethical issues of returning secondary pharmacogenomic variants in children undergoing genome sequencing. It offers considerations for clinicians and policymakers on routine screening and reporting these genetic findings.
Area of Science:
- Genomics and Health
- Bioethics
- Pediatric Medicine
Background:
- Children with serious diseases undergo exome/genome sequencing for diagnosis.
- Secondary pharmacogenomic variants may be incidentally found.
- Ethical, legal, and social implications (ELSI) of returning these findings are complex.
Purpose of the Study:
- To review ethical, legal, and social issues regarding the return of secondary pharmacogenomic variants in pediatric patients.
- To provide perspective on the clinical utility and implications of these findings.
- To inform policy and clinical practice regarding pharmacogenomic variant return.
Main Methods:
- Review of ethical, legal, and social issues.
- Discussion of active searching and reporting strategies.
- Analysis of data return, maintenance, decision support, and data sharing.
Main Results:
- Exploration of various methods for returning secondary pharmacogenomic findings.
- Consideration of long-term data maintenance in patient health records.
- Discussion on decision support tools for pharmacogenetic results.
Conclusions:
- Presents points to consider for clinicians and policymakers.
- Addresses the appropriateness of routine screening and return of pharmacogenomic variants.
- Highlights the need for careful deliberation on returning incidental pharmacogenomic findings in children.
Abstract:
This white paper was prepared by the Global Alliance for Genomics and Health Regulatory and Ethics Work Stream's Pediatric Task Team to review and provide perspective with respect to ethical, legal, and social issues regarding the return of secondary pharmacogenomic variants in children who have a serious disease or developmental disorder and are undergoing exome or genome sequencing to identify a genetic cause of their condition. We discuss actively searching for and reporting pharmacogenetic/genomic variants in pediatric patients, different methods of returning secondary pharmacogenomic findings to the patient/parents and/or treating clinicians, maintaining these data in the patient's health record over time, decision supports to assist using pharmacogenetic results in future treatment decisions, and sharing information in public databases to improve the clinical interpretation of pharmacogenetic variants identified in other children. We conclude by presenting a series of points to consider for clinicians and policymakers regarding whether, and under what circumstances, routine screening and return of pharmacogenomic variants unrelated to the indications for testing is appropriate in children who are undergoing genome-wide sequencing to assist in the diagnosis of a suspected genetic disease.
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