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MAPGen Mission

The traditional clinical/organ-system orientation of disease definitions groups patients with similar presentations, often ignoring differences in environmental exposures, clinical courses, and underlying pathobiology. Thus, patients with essentially different underlying pathologies will be grouped together under a common disease. This becomes problematic when patients with different underlying pathologies, but similar disease diagnoses, respond differentially to treatment. The focus on a subset of clinical manifestations leads to an oversimplified approach to disease definition and treatment and obscures possible pathogenetic overlaps among diseases as well as weakening genotype-phenotype correlations.

A new paradigm needs to be developed for characterizing research subjects, which will focus on phenotypic traits chosen to reflect fundamental biological processes, instead of the clinical symptoms of a traditionally defined organ system disease. Medicine has long recognized that diseases co-exist, one disease may have manifestations in multiple organs, or that one medication may affect multiple organ systems. Now there is increasing appreciation of the interconnectedness of traditionally defined diseases. Research discovery shows that many genes contribute to the manifestations of one traditionally defined disease, a single gene may be associated with more than one traditionally defined disease, and there are many connections among biological pathways.

Measures that define phenotype by mechanism across a wide range of study populations will yield a more integrated understanding of pathobiology across pre-disease and disease states, recognition of subpopulations within heterogeneous diseases, more precise use of molecular target-direct therapies, and, ultimately, stronger associations with genetic variants than have typically been found using disease-related phenotypes. The ultimate goal of this project is to achieve effective, personalized medical care through more precise identification of populations that will benefit from mechanism-based interventions for prevention and treatment.

This consortium seeks to identify and characterize common pathobiologic traits and/or mechanisms that cross organ systems and diseases with the ultimate goal of redefining heart, lung, blood, and sleep disorders based on newfound knowledge of the underlying molecular and/or cellular pathobiology. This will provide the basis for the rational, mechanism-based development of new diagnostic, prognostic and therapeutic strategies for heart, lung, blood and sleep disorders.