WP 2. Genes and environment as risk factors for development of rheumatic disease

This area of work will be lead by Partner 14 (Manchester) with input from Partner 1 (KI), 2 (Leiden), 6 (Amsterdam) and Partner 25 (BMD)

The Norfolk arthritis register includes close to 2000 individuals with early arthritis, identified in a population setting, and followed over several years with careful clinical as well as radiological investigations. Biological specimens for genotyping and serology have been obtained from approximately 500 of he patients. Detailed data on environmental exposures before onset of disease also exist.

The Swedish register on early arthritis (called the EIRA material) is comprised of approximately 2000 cases of newly onset RA, and populations-matched controls. The patients have been followed closely for disease course and medication. Both patients and the controls have answered an extensive questionnaire mapping environmental exposures before onset of disease. In addition almost all patients and most controls have donated blood samples for serology and genotyping (patients at their first visit to the clinic before medication). Cohorts in Leiden comprise 1800 patients with early arthritis followed for several years. Basic data concerning major risk factors such as smoking are available.

The project aims to fuse information from existing materials in order to allow us to get a unique power in studying genetic polymorphisms of importance both for onset of arthritis and for disease course. The combined materials will comprise the most extensive material in the world suitable for association studies on genetic polymorphisms associated with onset of disease. It will comprise the only material in the world where gene-environment interactions will be possible to study with a reasonable power.

A database would be constructed to allow pooling of all these datasets between countries and to identify those individuals who, according to robust definitions, remit very early on in the disease and those who develop into chronic rheumatoid arthritis. Within the first 18 months we aim to have the first results from the pooled data and be able to identify prognostic factors for disease remission as well as negative prognostic factors. Genotyping will have be started on the genetic material available, based on the candidate genes that have emerged from the other parts of the programme and the role of these candidates together with environmental factors, including details of treatment given, after adjusting for disease severity variables, on identifying these outcomes be considered will be identified.