WP4 - Interactions between genes and environment in the etiology of chronic inflammatory diseases

WP coordinator: Leonid Padyukov

Understanding interactions between genes, environment and immunity is key to deciphering the etiology of complex diseases. The work in WP 1-3 will provide general infrastructure support for studies in this area for several diseases, e. g. rheumatoid arthritis (RA), systemic lupus erythematosus, inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis. We have preliminary data on RA (a case-control study of 3000 patients and 3000 matched controls) demonstrating profound interactions between genes (HLA-DR, PTPN22), smoking and anti-citrulline immunity, where these studies have led to a formulation of workable hypothesis for a molecular pathogenesis of RA (Klareskog et al Arthritis & Rheumatism, 2006; Källberg et al, AJHG, 2007). A new finding on lifestyle that is of special interest is that moderate alcohol consumption is protective against arthritis in animals (Jonsson et al., PNAS, 2007) and is also associated with protection in human RA and SLE (Källberg et al. Ann Rheumatic Dis., 2008).

Finally, WP4 have access to data on wide genome scans (300,000 – 500,000 single nucleotide polymorphisms, SNPs) on large case control materials of RA (3000 individuals (Plenge, Seielstad et al, NEJM, 2007; Seielstad et al, manuscript in preparation), psoriasis (1000 individuals) and to IBD (1500 individuals).