2026-08-11 コロンビア大学
＜関連情報＞
- https://www.publichealth.columbia.edu/news/researchers-develop-new-computational-framework-identify-novel-pathway-asthma
- https://www.cell.com/cell/fulltext/S0092-8674(26)00866-4
トランス調節遺伝子マッピングにより喘息の疾患ドライバーが優先的に特定される Trans-regulatory gene mapping prioritizes disease drivers in asthma
Isabella M. Salamone ∙ Peixin Tian, ∙ Zining Qi ∙ … ∙ Zhonghua Liu ∙ Marcelo A. Nóbrega ∙ Xuanyao Liu
Cell Published:August 11, 2026
DOI:https://doi.org/10.1016/j.cell.2026.07.034
Highlights
- Integrating trans-regulatory signals and burden tests prioritizes disease-driving genes
- Prioritized genes are enriched for Mendelian genes missed by other genomics approaches
- CRISPR screens validate prioritized genes as regulators of key asthma cellular phenotypes
- Loss of palmitoylation enzymes SLC27A3 and SCD affects lung inflammation in vivo
Summary
Deciphering which genes are most important to disease etiology is a central challenge in human genetics. While genome-wide association studies have cataloged thousands of variants, it’s been proposed that most are indirect regulators of a limited, currently unidentified set of central disease-driving genes, defined here as disease-proximal genes (DPGs). Here, we introduce DANDELION, a mediation-inspired statistical framework that prioritizes DPGs by integrating trans-regulatory effects from disease-relevant tissues with gene-level burden from whole-exome sequencing. Applying DANDELION to asthma uncovers novel DPGs that escape detection by conventional methods. CRISPR screens in epithelial and T cells find that most DPGs regulate key asthma-related cellular phenotypes. We also demonstrate that loss of two DPGs, SLC27A3 and SCD, affects inflammation and airway remodeling in a mouse model of allergic asthma. Our study establishes DANDELION as a powerful framework for prioritizing novel, therapeutically actionable genes and pathways underlying disease pathogenesis.
