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High-throughput framework for genetic analyses of adverse drug reactions using electronic health records
- Source :
- PLoS Genetics, Vol 17, Iss 6, p e1009593 (2021), PLoS Genetics
- Publication Year :
- 2021
- Publisher :
- Public Library of Science (PLoS), 2021.
-
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.<br />Author summary Adverse drug reactions are a considerable burden on the healthcare system. Genetic studies can improve our understanding of the pathophysiological mechanisms of adverse drug reactions but have been hindered by small sample sizes. Drug responses are less often recorded than physiological traits and common diseases. Here, we present a high-throughput framework to efficiently identify eligible patients for genetic studies of adverse drug reactions from electronic health records. We validated our approach by conducting genome-wide association studies for adverse reactions to 14 common drug/drug groups with 81,739 individuals from Vanderbilt University Medical Centre’s BioVU DNA Biobank, identifying 7 genetic loci associated with adverse drug reactions. Our high-throughput framework can enable impactful pharmacogenomic research to help develop clinical guidelines for the delivery of the right drug to the right person.
- Subjects :
- Cancer Research
Electronic Medical Records
Genome-wide association study
QH426-470
Bioinformatics
030226 pharmacology & pharmacy
0302 clinical medicine
Antibiotics
Allergies
Medicine and Health Sciences
Electronic Health Records
Precision Medicine
Genetics (clinical)
Analgesics
0303 health sciences
Antimicrobials
Drug Information
Drugs
High-Throughput Nucleotide Sequencing
Genomics
Biobank
Information Technology
Research Article
Computer and Information Sciences
Drug-Related Side Effects and Adverse Reactions
Immunology
Drug allergy
MEDLINE
Biology
Microbiology
03 medical and health sciences
Adverse Reactions
Microbial Control
Genome-Wide Association Studies
Genetics
medicine
Pain Management
Humans
Molecular Biology
Alleles
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
Genetic association
Pharmacology
Biology and Life Sciences
Computational Biology
Health Information Technology
Human Genetics
Penicillin
Genome Analysis
Precision medicine
medicine.disease
Health Care
Opioids
Genetic Loci
Pharmacogenetics
Pharmacogenomics
Expression quantitative trait loci
Clinical Immunology
Clinical Medicine
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 15537404
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- PLOS Genetics
- Accession number :
- edsair.doi.dedup.....4d8c5e5614102f6e4bd8e032ddc8f3e9