Sex-dependent gene co-expression in the human body

Area of Science:

• Genomics
• Systems Biology
• Sex Differences in Biology

Background:

• Pathophysiological mechanisms in human health and disease are often sex-dependent.
• Systems biology approaches are valuable for understanding disease etiology.
• The impact of sex on gene network biology remains largely unexplored.

Purpose of the Study:

• To investigate the influence of sex on whole-body gene co-expression networks.
• To quantify sex differences in gene co-expression across multiple human tissues.
• To explore the implications of sex-biased gene networks in disease and drug targeting.

Main Methods:

• Utilized RNA-sequencing data from over 700 individuals (Genotype-Tissue Expression project).
• Generated a whole-body gene co-expression map across 24 tissues.
• Quantified sex-specific gene co-expression patterns and pathway enrichment.

Main Results:

• Sex influences 29.5% of analyzed gene co-expression across 24 tissues.
• Significant sex-biased gene co-expression observed in tissues like skeletal muscle (males) and thyroid (females).
• Sex differences in pathway enrichment (hypoxia, EMT, inflammation) and transcription factor binding motifs were identified.
• Sex-biased genes are linked to sex-biased diseases (autoimmunity, cancer) and are more frequently targeted by FDA-approved drugs.

Conclusions:

• Sex significantly shapes biological gene networks through differential gene co-expression.
• Sex-dependent biological responses, particularly to medical drugs, warrant further investigation.
• This study highlights the importance of considering sex as a biological variable in biomedical research.