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Related Concept Videos

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Related Experiment Video

Updated: Jan 8, 2026

Large-Scale Multi-Omics Genome-Wide Association Studies Mo-GWAS: Guidelines for Sample Preparation and Normalization
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Co-expression-wide association studies link genetically regulated interactions with complex traits.

Mykhaylo M Malakhov1, Wei Pan2

  • 1Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, MN, USA.

Nature Communications
|December 11, 2025
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Summary
This summary is machine-generated.

Introducing co-expression-wide association study (COWAS), a new method to find gene and protein pairs linked to complex traits. COWAS reveals how interacting proteins influence diseases, even when acting alone they don't.

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Area of Science:

  • Genetics and Systems Biology
  • Computational Biology
  • Disease Risk Prediction

Background:

  • Transcriptome- and proteome-wide association studies (TWAS/PWAS) identify genes/proteins linked to disease risk.
  • Existing methods overlook co-expression and interaction effects between genes or proteins.
  • Understanding molecular networks is crucial for complex trait genetics.

Purpose of the Study:

  • Introduce the co-expression-wide association study (COWAS) method.
  • Identify gene/protein pairs with genetically regulated co-expression associated with complex traits.
  • Investigate the role of protein-protein interactions in disease etiology.

Main Methods:

  • COWAS trains models to predict expression and co-expression from genetic variation.
  • Tests association between imputed co-expression and traits, accounting for direct effects.
  • Applies the method to UK Biobank plasma proteomic data.

Main Results:

  • Identified dozens of interacting protein pairs associated with cholesterol levels, Alzheimer's, and Parkinson's diseases.
  • Demonstrated that protein co-expression can influence complex traits independently of individual protein effects.
  • Showcased COWAS's ability to disentangle direct and interaction effects in molecular networks.

Conclusions:

  • COWAS provides a novel approach to uncover genetically regulated co-expression patterns associated with complex traits.
  • Protein-protein interactions revealed by COWAS offer new insights into disease mechanisms.
  • The method enhances understanding of molecular networks mediating genetic effects on disease.