CEHP Seminar - Jean-Baptiste Pingault

Title: Using genomics for drug discovery in psychiatry: principles and application to depression

Abstract:

Recent results demonstrate that drug targets with genetic support are 2.6 times more likely to receive marketing approval, and 63% of drugs approved by the FDA in the past decade had genetic evidence. Thus, genetic support can both accelerate discovery and reduce costs. Genetically informed methods for drug discovery leverage the fact that genes code for proteins, and >90% of existing drugs target proteins. We can thus use genetic variants as proxies to identify proteins relevant for disease endpoints. We can then check identified proteins against what is called the ‘druggable genome’, i.e. genes that code for proteins that are themselves potential targets of drugs. To that end, we use Mendelian randomisation, a genetically informed causal inference method.  Here, I will be presenting the principles of Mendelian randomisation, how it can be applied for drug discovery, as well as some of our findings resulting from implementing our pipeline using the latest Genome-Wide Association Study for Major Depressive Disorder (525k cases). We find genetic evidence supporting a large proportion of current drugs indicated for MDD (i.e. positive controls) as well as evidence for repurposing opportunities and novel compounds.