Abstract The genetic architecture of the different diseases and traits studied in the AMP projects are relatively well known and have continued to expand over time. While some causal modeling using LD score regression and other Mendelian Randomization techniques have been pursued in each disease to various extents; these efforts have not systematically looked at this collection of diseases together in a unified fashion. Further, we can enrich the deployment of these methods with up-to-date results with the genetic architecture of a variety of immune-related traits that have been mapped in the AMP projects as well as disease-related endophenotypes: single cell data from individual cell types from blood and tissue, modules of co-expressed genes, proteins and metabolites from tissue and blood, as well as individual genes, proteins or metabolites that may be of particular interest. We will therefore bring all up-to-date to bear on examining whether and how genetic susceptibility to a variety of inflammatory, metabolic, and neurologic diseases converge onto different immune responses in peripheral blood, other fluid compartments, and the target tissue of each disease.