Related Experiment Video
Updated: May 29, 2026
10:42
Generation and Culturing of Primary Human Keratinocytes from Adult Skin
Published on: December 22, 2017
Multicytokine-based transcriptome-wide association study for 7 inflammatory skin disorders identifies candidate
Haihan Zhang1, Matthew T Patrick2, Mrinal K Sarkar2
1Department of Biostatistics, University of Michigan, Ann Arbor, Mich.
The Journal of Allergy and Clinical Immunology
|May 27, 2026
Summary
Modeling gene expression across multiple conditions enhances transcriptome-wide association studies (TWAS) for identifying causal genes in inflammatory skin diseases. This approach improves power and resolution, revealing how genetic variants influence epithelial inflammation.
Area of Science:
- Genetics
- Immunology
- Dermatology
Background:
- Transcriptome-wide association studies (TWAS) typically use a single cellular context, limiting their ability to pinpoint causal genes.
- Genetically regulated expression (GReX) components are identified by TWAS, but context-specific limitations exist.
Purpose of the Study:
- To enhance the power of TWAS for identifying causal genes in complex inflammatory diseases by modeling GReX across multiple conditions.
- To investigate the role of GReX in seven inflammatory skin diseases.
Main Methods:
- Conducted TWAS on 400 transcriptomes under eight pro-inflammatory cytokine stimulations in keratinocytes.
- Modeled GReX for 18,599 genes against GWAS data from seven inflammatory skin diseases.
- Utilized single-cell resolution spatial profiling to validate findings in psoriatic skin.
Main Results:
- Identified 274 significant TWAS loci across seven inflammatory skin diseases.
- Nominated causal genes and associated cytokine stimuli, including ERAP2 (psoriasis), WNT10A (acne), and others for alopecia areata and SLE.
- Demonstrated strong colocalization of TWAS-identified genes with GWAS signals (p = 1.03×10-15) and captured over 85% of genes with colocalizing eQTLs.
Conclusions:
- Modeling gene expression across relevant cellular states significantly improves TWAS power and resolution.
- Genetic signals for skin conditions shape inflammatory responses in the epithelium, providing insights into how susceptibility loci modulate cytokine responses in keratinocytes.
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