A core assumption in the study of complex-disease-causing genes has been that they are clustered in molecular pathways directly connected to the disease. But work by a group of researchers at the Stanford University School of Medicine suggests otherwise. The gene activity of cells is so broadly networked that virtually any gene can influence disease, the researchers found. As a result, most of the heritability of complex diseases is due not to a handful of core genes, but to tiny contributions from vast numbers of peripheral genes that function outside disease pathways. Any given trait, it seems, is not controlled by a small set of genes. Instead, nearly every gene in the genome influences everything about us. The effects may be tiny, but they add up. The work is described in a Perspective piece published in the June 15, 2017 issue of Cell. Jonathan Pritchard (photo), PhD, Professor of Genetics and of Biology, is the senior author. Graduate student Evan Boyle and postdoctoral scholar Yang Li, PhD, share lead authorship. The article is titled “An Expanded View of Complex Traits: From Polygenic to Omnigenic.” The researchers call their provocative new understanding of complex disease genes an "omnigenic model" to indicate that almost any gene can influence complex diseases and other complex traits. In any cell, there might be 50 to 100 core genes with direct effects on a given complex trait, as well as easily another 10,000 peripheral genes that are expressed in the same cell with indirect effects on that complex trait, said Dr. Pritchard, who is also a Howard Hughes Medical Institute investigator.
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