The goal of this proposal is to develop support for an integrated institutional program on the genetics of human disease and complex traits. There is no more opportune time for this effort than the present: the combination of advances in sequencing the human genome and the increased availability of clinical datasets is now poised for integration using the capacities of molecular biology, computational sciences, and epidemiological and statistical principles. These approaches will generate important information on the genetic basis of human health and disease, which will enhance the diagnosis and therapy of disease, and advance the discovery of new targets and drugs. This goal is perfectly aligned with the three major themes of the NIH Roadmap: application of new scientific pathways to discovery, integration of clinical and basic research, and formation of interdisciplinary research teams. The University of Pennsylvania School of Medicine is one of the nation's premier biomedical research institutions. Penn is distinctly positioned to achieve success in this effort as the School and Health System are fully integrated at both leadership and operational levels. To achieve our goal we propose to unite critical interdisciplinary expertise in clinical and molecular informatics, with the methodologies of epidemiology and statistical genetics by formation of the Center for Human Genetics and Complex Traits. The Center will be located in newly renovated space (10,724 gsf) in Blocklev Hall. The primary missions of the Center are to apply this integrated approach across four disease-based themes, and to train new scientists with cross-disciplinary expertise.