Common Disease Is More Complex Than Implied by the Core Gene Omnigenic Model

Publication date: 14 June 2018 Source:Cell, Volume 173, Issue 7 Author(s): Naomi R. Wray, Cisca Wijmenga, Patrick F. Sullivan, Jian Yang, Peter M. Visscher 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. Teaser Frameworks for understanding how genes contribute to phenotypic traits have the power to shape experimental approaches and funding allocations. In contrast to the recent “omnigenic” model that emphasized contributions from a few core genes to complex disease, this Perspective argues for continued support for acquiring a broad range of patient data to link genetic variation with phenotypic diversity.

Source: Cell - June 15, 2018 Category: Cytology Source Type: research