Pharmacogenomic Insights in Psychiatric Care: Uncovering Novel Actionability, Allele-Specific CYP2D6 Copy Number Variation, and Phenoconversion in 15,000 Patients

Authors

Jai N Patel
Sarah A Morris
Raul Torres
Brooke Rhead
Chris Vlangos
Daniel J Mueller
Lisa C Brown
Hailey Lefkofsky
Muneer Ali
Francisco M De La Vega
Kathleen C Barnes
Anthony Zoghbi
Joseph D Stanton
Marcus A Badgeley

Publication Date

11-1-2024

Journal

Molecular Psychiatry

DOI

10.1038/s41380-024-02588-4

PMID

38783055

PMCID

PMC11541190

PubMedCentral® Posted Date

5-23-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Cytochrome P-450 CYP2D6, DNA Copy Number Variations, Alleles, Female, Male, Cross-Sectional Studies, Phenotype, Middle Aged, Pharmacogenetics, Adult, Pharmacogenomic Testing, Mental Disorders, Cytochrome P-450 CYP2C19, Haplotypes, Genotype, Aged, High-Throughput Nucleotide Sequencing

Abstract

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and phenotype assignment was impacted by CYP2D6 allele-specific CNVs in 2% of all patients. Of 4114 patients with medication data, 42% had CYP2D6 phenoconversion from drug interactions and 20% carried a novel CYP2C haplotype potentially altering actionability. A total of 87% had some form of potential actionability from genetic findings and/or phenoconversion. Genetic variation detected via next-generation sequencing led to phenotype reassignment in 22% of individuals overall (2% in CYP2D6 and 20% in CYP2C19). Ultimately, pharmacogenomic testing using next-generation sequencing identified potential actionability in most patients receiving psychiatric care. Early pharmacogenomic testing may provide actionable insights to aid clinicians in drug prescribing to optimize psychiatric care.