WP 11. Technologies – genetic analysis

This area of work will be lead by Partner 14 (Manchester) with input from Partner 1 (Karolinska Institute), Partner 2 (Leiden), Partner 3 (Berlin-Charite) and Partner 18 (Evry-Paris).

Initially the partners will identify the precise composition of the cohorts that will be used for the combined analysis of candidate genes. It will be important to identify appropriate numbers of cases and matched controls for which standardised clinical information is available. All cases will satisfy the recognised criteria for disease but in order to explore disease heterogeneity it will be necessary to identify subgroups of patients with specific disease characteristics. For example, different centres use different measures of rheumatoid factor, or erosions and initially the Partners must identify common factors that will allow merging of data from different centres.

The next step will be to identify appropriate candidate genes for investigation and to define the precise polymorphisms in these genes to be analysed. This will require variable amounts of genotyping to be carried out in the different centres depending on the data already obtained. Researchers in the different centres will work together to analyse the data. Of particular interest will be the use of the longitudinal data to investigate rate of disease progression and outcome. Another unique feature of the study will be the opportunity to investigate interactions between genes and between genes and environmental factors. Initially, interactions between new genes and HLA-DRB1 will be investigated.

The candidate genes selected for investigation will depend on the state of knowledge at the time of commencement of the investigation but at this stage it is anticipated that the first three genes to be targeted will be PADI4, SLC22A4 and PTPN22.