For nearly 20 years, our lab is focusing on aetiology of a complex disease, rheumatoid arthritis. After a period consisted of 'classical' genetic analyses through linkage and association studies, the GWAS results and conclusion lead us to develop alternative approaches. Instead of considering common genomic variants we decided to focus one rare and specific ones. We also extended our goal of RA biomarkers characterization to a transcriptome level. And we develop a global approach of the disease with mapping all the connections. For the next period of five years, and based to these approaches, we wish to develop our research activity in two main axes: characterization of new RA genomic variants and a computational systems biology approach that involves an interactive map and a dynamical model. Results of the first axe will feed the second project, the purpose of which is to be a tool for identifying new lines in RA drug design.