Objective

: Chronic pain is a significant rising cause of disability globally and the currently available drugs for its treatment have both poor efficacy and undesirable side effects. The term chronic pain comprises a heterogenous range of idiopathic disorders, which carry a moderate heritability, but have to date, with the exception of migraine, not proved amenable to GWAS approaches for the discovery of genetic associations. At Open Targets we are identifying novel molecular drug targets for the treatment of pain through a combination of human genetics and in vitro disease modelling. This group are undertaking several GWAS using UK Biobank pain data and have discovered several genome-wide significant loci associated with chronic pain. I will discuss these findings and present ongoing work to screen for new pain targets in vitro through genome-wide CRISPR-Cas9 gene editing in a human iPSC-derived sensory neuron model. The use of common natural genetic variation and genetic engineering, is an important new step for the systematic and rational identification of new pain targets.