Leveraging human genetics to guide drug target discovery

Identifying appropriate molecular targets is a critical step in drug development. Despite many advantages, the traditional tools of observational epidemiology and cellular or animal models of disease can be misleading in identifying causal pathways likely to lead to successful therapeutics. Here, we review some favorable aspects of human genetics studies that have the potential to accelerate drug target discovery. These include using genetic studies to identify pathways relevant to human disease, leveraging human genetics to discern causal relationships between biomarkers and disease, and studying genetic variation in humans to predict the potential efficacy and safety of inhibitory compounds aimed at molecular targets. We present some examples taken from studies of plasma lipids and coronary artery disease to highlight how human genetics can accelerate therapeutics development.