Genome-wide association study of medication-use and associated disease in the UK Biobank

Abstract

Genome-wide association studies (GWASs) of medication use may contribute to understanding of disease etiology, could generate new leads relevant for drug discovery and can be used to quantify future risk of medication taking. Here, we conduct GWASs of self-reported medication use from 23 medication categories in approximately 320,000 individuals from the UK Biobank. A total of 505 independent genetic loci that meet stringent criteria (P < 10⁻⁸/23) for statistical significance are identified. We investigate the implications of these GWAS findings in relation to biological mechanism, potential drug target identification and genetic risk stratification of disease. Amongst the medication-associated genes are 16 known therapeutic-effect target genes for medications from 9 categories. Two of the medication classes studied are for disorders that have not previously been subject to large GWAS (hypothyroidism and gastro-oesophageal reflux disease).

An understanding of the genetic variants associated with medication use may shed light on the underlying biological pathways of disease, and aid in drug development. Here, Wu and colleagues conduct a GWAS for self-reported medication-use in the UK Biobank, finding more than 500 independent variants and many promising leads for future work.