An Expanded View of Complex Traits: From Polygenic to Omnigenic

Area of Science:

• Genetics
• Systems Biology
• Genomics

Background:

• Understanding the genetic basis of complex diseases is a central goal in genetics.
• Traditionally, disease variants were expected to cluster in key etiological pathways.
• However, association signals for complex traits often distribute broadly across the genome.

Purpose of the Study:

• To propose and define an alternative model for the genetic architecture of complex traits.
• To explain why association signals are widespread and include genes not obviously linked to disease.

Main Methods:

• The study proposes a theoretical framework, the "omnigenic" model.
• This model posits that gene regulatory networks are highly interconnected.

Main Results:

• The omnigenic model suggests that all genes expressed in disease-relevant cells can influence core disease genes.
• It posits that most heritability for complex traits arises from effects on genes outside of traditionally defined core pathways.

Conclusions:

• The "omnigenic" model provides a unifying framework for understanding the genetic basis of complex traits.
• This perspective challenges the traditional view and highlights the pervasive influence of genetic variation across the genome.