Genetic susceptibility to rheumatoid arthritis and its implications for novel drug discovery.

INTRODUCTION: Over 100 susceptibility loci have now been identified for rheumatoid arthritis (RA), several of which are already the targets of approved RA therapies providing proof of concept for the use of genetics in novel drug development for RA. Determining how these loci contribute to disease will be key to elucidating the mechanisms driving disease development, which has the potential for major impact on therapeutic development. AREAS COVERED: Here the authors review the use of genetics in drug discovery, including the use of 'omics' data to prioritise potential drug targets at susceptibility loci using RA as an exemplar. They discuss the current state of RA genetics its impact on stratified medicine, and how the findings from RA genetics studies can be used to inform drug discovery. EXPERT OPINION: It is anticipated that functional characterisation of disease variants will provide biological validation of a gene as a drug target, providing safer targets, with an increased likelihood of efficacy. In the future, techniques such as genome editing may represent a plausible option for RA therapy. Technologies such as genome-wide chromatin conformation capture Hi-C and CRISPR will be crucial to inform our understanding of how diseases develop and in developing new treatments.