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Updated: Sep 12, 2025

Large-Scale Multi-Omics Genome-Wide Association Studies Mo-GWAS: Guidelines for Sample Preparation and Normalization
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Exploring the omnigenic architecture of selected complex traits.

Florin Ratajczak1, Matthias Heinig2, Pascal Falter-Braun3

  • 1Institute of Network Biology (INET), Molecular Targets and Therapeutics Center (MTTC), Helmholtz Center Munich, German Research Center for Environmental Health, Munich-Neuherberg, Germany.

American Journal of Human Genetics
|August 5, 2025
PubMed
Summary
This summary is machine-generated.

This study identifies core genes in ulcerative colitis (UC) using the Speos framework, revealing their central role in molecular networks and coordinated regulation across traits. These findings advance the omnigenic model by highlighting genetic interactions among core genes.

Keywords:
GWAScore genescoronary artery diseasegraph neural networksomnigenic modelschizophreniaulcerative colitis

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Area of Science:

  • Genetics
  • Systems Biology
  • Immunology

Background:

  • Genome-wide association studies (GWASs) identify thousands of trait-influencing loci.
  • The omnigenic model proposes core and peripheral genes affecting molecular traits.
  • Identifying core genes and their regulatory networks remains challenging.

Purpose of the Study:

  • To identify core genes for ulcerative colitis (UC) using the Speos framework.
  • To explore regulatory relationships between core and peripheral genes in multi-modal molecular networks.
  • To investigate the functional properties and network organization of core genes.

Main Methods:

  • Application of the Speos framework to identify core genes in UC.
  • Analysis of tissue-specific expression and network connections of identified core genes.
  • Utilizing genome-scale perturbation data (overexpression/knockdown) to assess gene responses.
  • Performing co-perturbation simulations to explore genetic interactions.

Main Results:

  • Core genes exhibit tissue-specific expression and trait-relevant network connections.
  • One-third of perturbations affected core genes differently than peripheral genes, a robust pattern across traits.
  • Co-perturbation simulations suggest frequent genetic interactions between core genes.
  • Core genes demonstrate coordinated regulation within molecular networks.

Conclusions:

  • Physiologically relevant core genes are central to molecular networks and exhibit coordinated genome-wide regulation.
  • The identified properties of core genes support and extend the omnigenic model.
  • Findings provide a foundation for quantitative analyses of core gene regulation and heritability.