A unified mapping framework of multifaceted pharmacodynamic responses to hypertension interventions

Abstract

The personalized therapy for hypertension needs comprehensive knowledge about how blood pressures (BPs; systolic and diastolic) and their pulsatile and steady components are controlled by genetic factors. Here, we propose a unified pharmacodynamic (PD) functional mapping framework for identifying specific quantitative trait loci (QTLs) that mediate multivariate response-dose curves of BP. This framework can characterize how QTLs govern pulsatile and steady components through jointly regulating systolic and diastolic pressures. The model can quantify the genetic effects of individual QTLs on maximal drug effect, the maximal rate of drug response, and the dose window of maximal drug response. This unified mapping framework provides a tool for identifying pharmacological genes potentially useful to design the right medication and right dose for patients.