Drug Response Pharmacogenetics for 200,000 UK Biobank Participants

Pharmacogenetics studies how genetic variation leads to variability in drug response. Guidelines for selecting the right drug and right dose for patients based on their genetics are clinically effective, but are widely unused. For some drugs, the normal clinical decision making process may lead to the optimal dose of a drug that minimizes side effects and maximizes effectiveness. Without measurements of genotype, physicians and patients may adjust dosage in a manner that reflects the underlying genetics. The emergence of genetic data linked to longitudinal clinical data in large biobanks offers an opportunity to confirm known pharmacogenetic interactions as well as discover novel associations by investigating outcomes from normal clinical practice. Here we use the UK Biobank to search for pharmacogenetic interactions among 200 drugs and 9 genes among 200,000 participants. We identify associations between pharmacogene phenotypes and drug maintenance dose as well as differential drug response phenotypes. We find support for several known drug-gene associations as well as novel pharmacogenetic interactions.