Phenotypic and genetic markers are urgently needed in autoimmune diseases for early and accurate diagnosis and monitoring disease progression and therapeutic intervention. We are proposing comprehensive phenotypic analysis for the identification of biological markers and genetic mapping of these quantifiable inheritable traits. Rheumatoid Arthritis (RA), a chronic inflammatory disorder that preferentially affects women will serve as a model disease. This application describes SurroMed's comprehensive phenotyping platform and the power of genetic analysis conducted at Myriad Genetics using a rich resource of family material. Phase I focuses on recruitment of RA multi-case families, technology development, and an initial analysis of human serum from affected RA family members and unaffected first-degree relatives. The approach includes both broad discovery-based and hypothesis-driven strategies. We will test the hypothesis that there are multiple quantitative differences in cellular and serum phenotypic variables between RA subjects and unaffected first-degree relatives. If our efforts are successful, in Phase II, we will test the hypothesis that variation in the levels of multiple biomarkers are significantly inheritable. Potential results of the work include biomarker and genetic products for the clinical assessment of disease. The methods developed here will also be broadly applicable to other conditions, especially autoimmune and immunological diseases. ? ?