LPAandAPOEare associated with statin selection in the UK Biobank

Abstract

AbstractGenetics plays a key role in drug response, affecting efficacy and toxicity. Pharmacogenomics aims to understand how genetic variation influences drug response and develop clinical guidelines to aid clinicians in personalized treatment decisions informed by genetics. Although pharmacogenomics has not been broadly adopted into clinical practice, genetics influences treatment decisions regardless. Physicians adjust patient care based on observed response to medication, which may occur as a result of genetic variants harbored by the patient. Here we seek to understand the genetics of drug selection in statin therapy, a class of drugs widely used for high cholesterol treatment. Genetics are known to play an important role in statin efficacy and toxicity, leading to significant changes in patient outcome. We performed genome-wide association studies (GWAS) on statin selection among 59,198 participants in the UK Biobank and found that variants known to influence statin efficacy are significantly associated with statin selection. Specifically, we find that carriers of variants inAPOEandLPAthat are known to decrease efficacy of treatment are more likely to be on atorvastatin, a stronger statin. Additionally, carriers of theAPOEandLPAvariants are more likely to be on a higher intensity dose (a dose that reduces low-density lipoprotein cholesterol by greater than 40%) of atorvastatin than non-carriers (APOE:p(high intensity)= 0.16, OR = 1.7,P= 1.64 × 10−4,LPA:p(high intensity)= 0.17, OR = 1.4,P= 1.14 × 10−2). These findings represent the largest genetic association study of statin selection and statin dose association to date and provide evidence for the role ofLPAandAPOEin statin response, furthering the possibility of personalized statin therapy.