Does Phenotypic Effect Size Reflect Upstream–Downstream Gene Hierarchy?

[akikuno]

📋 Description

Is the magnitude of phenotypic effect size indicative of hierarchical relationships among genes within biological pathways or regulatory networks?

Background

Intuitively, genes with larger phenotypic effect sizes may be interpreted as having stronger functional influence. One possible interpretation is that genes producing larger effects might be positioned upstream in regulatory or signaling cascades, thereby impacting multiple downstream components.

However, it remains unclear whether phenotypic effect size reliably reflects such upstream–downstream relationships, or whether it is influenced by other factors such as network redundancy, compensatory mechanisms, or measurement biases.

Questions

• Can phenotypic effect size be used as a proxy for estimating gene hierarchy within biological pathways?
• Are there known studies or theoretical frameworks that support or refute this assumption?
• What confounding factors should be considered when interpreting effect size as evidence of upstream regulatory influence?

Expected Outcome

Clarifying whether effect size can serve as a biologically meaningful indicator of gene hierarchy would help improve interpretation of phenotype-driven gene network analyses.

🔖 TSUMUGI Version

No response

📎 Anything else?

This idea originated from Dr. Hayate Suzuki. Thank you!