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The evidence that most adult-onset common diseases have a polygenic genetic architecture fully consistent with robust biological systems supported by multiple back-up mechanisms is now overwhelming. In this context, we consider the recent "omnigenic" or "core genes" model. A key assumption of the model is that there is a relatively small number of core genes relevant to any disease. While intuitively appealing, this model may underestimate the biological complexity of common disease, and therefore, the goal to discover core genes should not guide experimental design. We consider other implications of polygenicity, concluding that a focus on patient stratification is needed to achieve the goals of precision medicine.

Original publication




Journal article



Publication Date





1573 - 1580


Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, Australia. Electronic address:


Humans, Disease, Multifactorial Inheritance, Models, Genetic, Genome-Wide Association Study, Precision Medicine