An Expanded View of Complex Traits: From Polygenic to Omnigenic

Cell. 2017 Jun 15;169(7):1177-1186. doi: 10.1016/j.cell.2017.05.038.

Abstract

A central goal of genetics is to understand the links between genetic variation and disease. Intuitively, one might expect disease-causing variants to cluster into key pathways that drive disease etiology. But for complex traits, association signals tend to be spread across most of the genome-including near many genes without an obvious connection to disease. We propose that gene regulatory networks are sufficiently interconnected such that all genes expressed in disease-relevant cells are liable to affect the functions of core disease-related genes and that most heritability can be explained by effects on genes outside core pathways. We refer to this hypothesis as an "omnigenic" model.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease / genetics*
  • Genetic Diseases, Inborn / genetics
  • Genome-Wide Association Study
  • Genomics
  • Humans
  • Multifactorial Inheritance*
  • Polymorphism, Single Nucleotide