2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Estimating UK Biobank population-specific PGx allele and phenotype frequencies using PharmCAT

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This document discusses the use of the Pharmacogenomics Clinical Annotation Tool (PharmCAT) to estimate population-specific pharmacogenomics (PGx) frequencies using UK Biobank data. The study focused on estimating PGx frequencies for sixteen genes in five biogeographic populations. The analysis included rare PGx alleles that had been rarely reported or tested by genetic tests in certain populations. The estimated frequencies will be shared on the PharmGKB website. Next steps include expanding the analysis to the whole 500K UK Biobank data and investigating novel partial or combination alleles. <br /><br />Pharmacogenomics is important for precision medicine, providing genotype-based drug prescribing recommendations. Estimating PGx allele and phenotype frequencies in different populations contributes to the design of clinical genetic tests and clinical practice. Previous studies have been limited in sample size and the subset of alleles studied. <br /><br />The study utilized the PharmCAT tool on the UK Biobank 200K integrated genetic call set to estimate PGx frequencies. Over 400 alleles and phenotypes were estimated in six populations. Figures show the distribution of allele function and phenotype for genes such as CYP2C9, CYP2C19, and SLCO1B1 across different populations. Guidelines are available for drugs related to these genes. The PharmCAT analysis complements frequency estimates for rare alleles that had been rarely reported or tested in certain populations. <br /><br />The UK Biobank 200K genetic data sets included whole-exome sequencing, imputed data, and microarray chip genotypes. Self-reported ethnicities were mapped to biogeographic populations. Quality control procedures were applied, and PharmCAT was used to estimate PGx frequencies. <br /><br />Overall, this study demonstrates the use of PharmCAT in estimating population-specific PGx frequencies using UK Biobank data and provides valuable insights for precision medicine and clinical practice.

Asset Subtitle

Submitter Only - Binglan Li, PhD; Co-Author - Katrin Sangkuhl, PhD; Co-Author - Ryan Whaley, BS; Co-Author - Mark Woon, BS; Co-Author - Karl Keat, BS; Presenting Author - Li Gong, PhD; Co-Author - Michelle Whirl-Carrillo, PhD; Co-Author - Marylyn D. Ritchie, PhD; Co-Author - Teri E. Klein;

Meta Tag

Pharmacogenomics

Population Genetics

Co-Author Katrin Sangkuhl, PhD

Co-Author Ryan Whaley, BS

Co-Author Mark Woon, BS

Co-Author Karl Keat, BS

Co-Author Michelle Whirl-Carrillo, PhD

Co-Author Marylyn D. Ritchie, PhD

Co-Author Teri E. Klein

Presenting Author Li Gong, PhD

Submitter Only Binglan Li, PhD

Keywords

Pharmacogenomics Clinical Annotation Tool

PharmCAT

population-specific pharmacogenomics frequencies

UK Biobank data

rare PGx alleles

genetic tests

precision medicine

clinical genetic tests

CYP2C9

CYP2C19