A Pilot Study for Return of Individual Pharmacogenomic Results to Population-Based Cohort Study Participants

Abstract

Introduction: Pharmacogenomic (PGx) testing results provide valuable information on drug selection and appropriate dosing, maximization of efficacy, and minimization of adverse effects. Although the number of large-scale, next-generation-sequencing-based PGx studies has recently increased, little is known about the risks and benefits of returning PGx results to ostensibly healthy individuals in research settings. Methods: Single-nucleotide variants of three actionable PGx genes, namely, MT-RNR1 , CYP2C19 , and NUDT15 , were returned to 161 participants in a population-based Tohoku Medical Megabank project. Informed consent was obtained from the participants after a seminar on the outline of this study. The results were sent by mail alongside sealed information letter intended for clinicians. As an exception, genetic counseling was performed for the MT-RNR1 m.1555A > G variant carriers by a medical geneticist, and consultation with an otolaryngologist was encouraged. Questionnaire surveys (QSs) were conducted five times to evaluate the participants’ understanding of the topic, psychological impact, and attitude toward the study. Results: Whereas the majority of participants were unfamiliar with the term PGx, and none had undergone PGx testing before the study, more than 80% of the participants felt that they could acquire basic PGx knowledge sufficient to understand their genomic results and were satisfied with their potential benefit and use in future prescriptions. On the other hand, some felt that the PGx concepts or terminology was difficult to fully understand and suggested that in-person return of the results was desirable. Conclusions: These results collectively suggest possible benefits of returning preemptive PGx information to ostensibly healthy cohort participants in a research setting.

Biobanking as a Tool for Genomic Research: From Allele Frequencies to Cross-Ancestry Association Studies

“…The second pilot experiment was devoted to implementing pharmacogenomics results into clinical practice. Persons, who were identified as carriers of polymorphisms in the chosen genes-MT-RNR1, CYP2C19, or NUDT15-received recommendations both for themselves and healthcare workers [54].…”

Stakeholder Perception of the Implementation of Genetic Risk Testing for Twelve Multifactorial Diseases

“…Currently, studies on the practical application of PRSbased risk prediction for multifactorial diseases are mainly conducted in Europe and the United States [11][12][13][14]. The Tohoku Medical Megabank (TMM) Project [15] conducted a study on risk assignment based on genetic information for monogenic diseases, familial hypercholesterolemia, hereditary breast and ovarian cancer syndromes, and multiple drug susceptibilities and verified the clinical usefulness and feasibility of the risk assignment system [16][17][18]. We are currently conducting a PRS-based disease risk allocation study for multifactorial diseases in a larger target population.…”