Comment on: An Expanded View of Complex Traits: From Polygenic to Omnigenic

Xin He

doi:10.20900/jpbs.20170014s2

Abstract

Comment on: An Expanded View of Complex Traits: From Polygenic to Omnigenic

Highlights

The recent paper by Pritchard and colleagues proposed an “omnigenic” model to explain genetic architecture of complex human traits
The model states that a trait may be directly affected by a small set of “core genes”, but many other genes may perturb the activity of the core genes because of the inter-connectivity of biological networks
Acknowledging that there are a set of core genes of a disease, many other genes may affect the disease risk, not through acting on core genes, but by altering cellular states: how fast cells divide, how tolerant they are to stress, how quickly they respond to hormones, etc

Summary

Introduction

The recent paper by Pritchard and colleagues proposed an “omnigenic” model to explain genetic architecture of complex human traits. The model states that a trait may be directly affected by a small set of “core genes”, but many other genes may perturb the activity of the core genes because of the inter-connectivity of biological networks. It explains why genes found in rare variant studies often have clear disease connection while GWAS do not (only large-effect genes can be found in rare variant studies because of lower power); why variants often have pleiotropic effects on multiple traits; and why polygenic adaptation is common.

Results

Conclusion