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The polygenic, omnigenic and stratagenic models of complex disease risk.

Nature genetics - 1 Feb 2026

García-González Judit, O'Reilly Paul F

Abstract excerpt

A key goal of human genetics research is to understand how the effects of genetic variants combine to produce the risk of complex disease. Here we discuss and contrast three conceptual models developed to explain how multigenic risk is generated. The polygenic model, derived from the century-old infinitesimal model, has been the dominant framework for understanding the genetic inheritance of complex traits. More...

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PMID: 41559216
DOI: 10.1038/s41588-025-02467-w

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