The focus of my research program is the genetics and epidemiology of human autoimmune disease, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). My research unit has devoted substantial effort to the performance of genome wide association (GWA) and other genetics studies, which have led to the identification of over 30 genes that contribute to risk and outcome of these disorders. This work has also highlighted key biologic pathways responsible for disease onset and progression, which can inform more basic research to define the mechanism of these genetic associations. Given the heterogeneity of these disorders, we are also devoting substantial effort to the refinement of genotype-phenotype associations, such as the specificity of genetic associations for serologic or clinical subphenotypes. Several genes we have been studying, including STAT4 and TNFAIP3, are also of interest due to emerging evidence supporting their association with multiple autoimmune disorders and phenotypes. Given the strong association of the major histocompatibility complex (MHC) region with multiple autoimmune disorders, we are performing fine mapping studies of this region in order to further define the complex genetic associations of this region with SLE, RA and related phenotypes. We are also pursuing studies designed to better understand ethnic differences in autoimmune disease risk and outcome. Lastly, we have initiated several recent studies that seek to define the contribution of epigenetic factors, particularly DNA methylation patterns, to autoimmune disease risk and outcome.