Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 60,239 bioRxiv papers from 267,831 authors.

Trans effects on gene expression can drive omnigenic inheritance

By Xuanyao Liu, Yang I Li, Jonathan K Pritchard

Posted 24 Sep 2018
bioRxiv DOI: 10.1101/425108 (published DOI: 10.1016/j.cell.2019.04.014)

Early genome-wide association studies (GWAS) led to the surprising discovery that, for typical complex traits, the most significant genetic variants contribute only a small fraction of the estimated heritability. Instead, it has become clear that a huge number of common variants, each with tiny effects, explain most of the heritability. Previously, we argued that these patterns conflict with standard conceptual models, and that new models are needed. Here we provide a formal model in which genetic contributions to complex traits can be partitioned into direct effects from core genes, and indirect effects from peripheral genes acting as trans-regulators. We argue that the central importance of peripheral genes is a direct consequence of the large contribution of trans-acting variation to gene expression variation. In particular, we propose that if the core genes for a trait are co-regulated - as seems likely - then the effects of peripheral variation can be amplified by these co-regulated networks such that nearly all of the genetic variance is driven by peripheral genes. Thus our model proposes a framework for understanding key features of the architecture of complex traits.

Download data

  • Downloaded 3,565 times
  • Download rankings, all-time:
    • Site-wide: 762 out of 60,239
    • In genetics: 75 out of 3,435
  • Year to date:
    • Site-wide: 802 out of 60,239
  • Since beginning of last month:
    • Site-wide: 4,430 out of 60,239

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)


News