Sarcoidosis and AAT are pulmonary diseases for which there is no cure and current medical therapies are not effective in many patients. The GRADS initiative represents a tremendous opportunity to advance the knowledge of these diseases using state-of-the-art techniques to phenotype subjects and analyze biospecimens. The University of California, San Francisco (UCSF) and University of Illinois at Chicago (UIC) centers have joined together in this application to present genomic, genetic and immunophenotyping data which demonstrate clinical and experimental expertise as well as novel hypotheses related to understanding disease mechanisms and phenotypes of sarcoidosis. We propose a Study-Wide protocol in Aim 1 to phenotype both sarcoidosis and AAT subjects using cutting-edge technologies ranging from genomics (including miRNA analyses) to multi-parameter immunophenotyping, and detailed clinical phenotyping. We also propose two Center-Specific studies focused on sarcoidosis that synergize with the Study-Wide protocol, by adding numerous samples from well-phenotyped subjects with sarcoidosis that will increase the robustness and quality of the study findings. Aim 2 is focused on genomics (mRNA and miRNA) and immunophenotyping to address several questions including the identification of a novel set of genomic markers that track with disease severity and may be markers of disease progression and/or activity. In addition, studies proposed in Aim 2 will identify the specific T cell miRNAs that are abnormally regulated in BAL cells in sarcoidosis and relate these findings to T cell phenotype and effector function. In Aim 3, we will validate a panel of ~300 SNPs identified by GWAS, eQTL and candidate gene approaches, which associate with susceptibility to sarcoidosis and risk for complicated sarcoidosis (pulmonary, cardiac, neurosarcoidosis). Together, these studies have the capacity of identifying novel targets, novel biomarkers, novel phenotyping tools and likely innovative therapeutic strategies for the enigmatic disorder known as sarcoidosis.