Genome-wide associations spanning 194 in-hospital drug dosage change phenotypes highlight diverse genetic backgrounds in concurrent drug therapy
Year: 2025
Type: article
Study design: Observational Study
Abstract: As populations get older and medicine consumption rises, the rate of concurrent drug use and polypharmacy among patients is increasing. Polypharmacy is known to complicate therapy and increase the risk of drug-drug interactions, the individuality of which remain largely unexplored. Here, we perform a series of genome-wide association studies to identify variants associated with dosage changes during episodes of concurrent drug therapy. We extracted in-hospital drug prescription records from 847,537 patients in a population-wide Danish hospital cohort. Using imputed genotype data from the Copenhagen Hospital Biobank and the Danish Blood Donor Study we then performed a series of genome-wide association analyses across 194 drug pair phenotypes fulfilling selection criteria. We identified 51 genome-wide significant (p < 5E-08) loci, 49 so far unreported in any genome-wide association studies, associated with dosage changes across 42 different drug pair phenotypes. 49 of the identified loci were unique to the respective drug pairs. Through annotation of the identified loci, expression quantitative trait loci analyses, and gene-based tests we found links to 57 distinct genes, several of which have previously been associated with disease. This study identifies genes that may modulate response to drug therapy in the context of polypharmacy. Our findings reveal distinct patterns of genetic variation across different drug pairs, suggesting a diverse set of genes involved in drug efficacy and drug response. This study may give a better understanding of the individuality of such mechanisms and may aid the development personalized treatment approaches.
Authors: Alexander Pil Henriksen, Cristina Leal Rodríguez, Hannah Currant, Ioannis Louloudis, Jorge Hernansanz Biel, Maria Herrero-Zazo, Ewan Birney, Thomas Folkmann Hansen, Gianluca Mazzoni, Amalie Dahl Haue, Henning Bundgaard, Christian Erikstrup, Khoa Manh Dinh, Liam Quinn, Mie Topholm Bruun, Henrik Hjalgrim, Erik Sørensen, Christina Mikkelsen, Michael Schwinn, Ole Birger Vestager Pedersen, Henrik Ullum, Sisse Rye Ostrowski, Karina Banasik, Søren Brunak
Institutions: University of Copenhagen, Novo Nordisk Foundation, Gentofte Hospital, Copenhagen Prospective Studies on Asthma in Childhood, University of Oxford, European Bioinformatics Institute, Copenhagen University Hospital, Rigshospitalet, Aarhus University, Aarhus University Hospital, Zealand University Hospital Køge, Odense University Hospital, Statens Serum Institut, Danish Cancer Society, Hvidovre Hospital
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,230
OpenAlex ID: W4411634851