Trans-eQTLs Can Be Used to Identify Tissue-Specific Gene Regulatory Networks.

Area of Science:

• Genetics
• Systems Biology
• Bioinformatics

Background:

• Previous studies suggest trans-eQTLs (expression quantitative trait loci) are tissue-specific.
• Identifying tissue-specific gene regulatory networks is crucial for understanding complex biological processes.

Purpose of the Study:

• To investigate if tissue-specific trans-eQTLs can be used to identify gene regulatory networks.
• To characterize the properties and functions of these networks.

Main Methods:

• Utilized eQTL data from eQTLGen and INTERVAL studies.
• Selected cis- and trans-eQTLs (p < 5 × 10⁻⁸) and performed Mendelian randomization.
• Analyzed network topology and gene functions.

Main Results:

• Detected trans-regulatory impact of 138 genes on 342 genes (p < 5 × 10⁻⁸).
• Identified gene networks with scale-free topology, primarily involved in immune processes.
• Hub genes, like DDAH2, showed transcription regulation activity and were linked to blood cell traits and disorders.

Conclusions:

• Tissue-specific gene regulatory networks can be identified through their genomic underpinnings.
• The scale-free topology suggests hub genes are key targets for correcting abnormalities.
• Findings provide insights into genetic regulation of immune and metabolic processes.