High-throughput framework for genetic analyses of adverse drug reactions using electronic health records

PLoS Genet. 2021 Jun 1;17(6):e1009593. doi: 10.1371/journal.pgen.1009593. eCollection 2021 Jun.

Abstract

Understanding the contribution of genetic variation to drug response can improve the delivery of precision medicine. However, genome-wide association studies (GWAS) for drug response are uncommon and are often hindered by small sample sizes. We present a high-throughput framework to efficiently identify eligible patients for genetic studies of adverse drug reactions (ADRs) using "drug allergy" labels from electronic health records (EHRs). As a proof-of-concept, we conducted GWAS for ADRs to 14 common drug/drug groups with 81,739 individuals from Vanderbilt University Medical Center's BioVU DNA Biobank. We identified 7 genetic loci associated with ADRs at P < 5 × 10-8, including known genetic associations such as CYP2D6 and OPRM1 for CYP2D6-metabolized opioid ADR. Additional expression quantitative trait loci and phenome-wide association analyses added evidence to the observed associations. Our high-throughput framework is both scalable and portable, enabling impactful pharmacogenomic research to improve precision medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Drug-Related Side Effects and Adverse Reactions / genetics*
  • Electronic Health Records*
  • Genome-Wide Association Study
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Pharmacogenetics
  • Precision Medicine