A research team led by Hong-Hee Won from Sungkyunkwan University has pinpointed the genetic and cellular mechanisms underlying psoriasis by combining genomic data from more than 1.1 million people with single-cell analysis of patient skin samples. The findings, published in Nature Communications, also flag a slate of genes as candidate targets for new treatments.
Genetic and cellular studies of psoriasis have largely proceeded on separate tracks, with few efforts linking large-scale genomic findings to what individual cells are actually doing in diseased tissue. To close that gap, the team ran an integrated meta-analysis of genomic data from the 1.1 million-person cohort—all of European ancestry—and identified 125 independent genetic susceptibility loci associated with the disease. Seventeen of those loci had never been reported before.
The team then layered single-cell transcriptomic analysis on top of the genetic findings, examining gene activity at single-cell resolution in skin samples from both healthy individuals and psoriasis patients. That combination let them trace which specific cell populations are actually driving disease onset, rather than just which genes are statistically associated with it.
The single-cell data revealed a complex signaling interplay among several cell types: myeloid cells and T cells from the immune system, keratinocytes on the skin’s surface, and vascular endothelial cells lining blood vessels. These populations appear to interact in a cascade that fuels excessive inflammation. By mapping how these cell types interact across different skin layers—comparing non-lesional, lesional, and treated tissue—the researchers narrowed the field to 50 promising therapeutic target genes, each showing cell subtype-specific activity patterns.
“This research combines large-scale genomic data with precise cellular transcriptomic analysis to clearly reveal which genetic factors and cell types are involved in psoriasis pathology,” said Professor Won. “We expect our findings to serve as a key milestone in developing personalized immune-modulating treatments and new drugs tailored to individual patients.”
Genetic and cellular studies of psoriasis have largely proceeded on separate tracks, with few efforts linking large-scale genomic findings to what individual cells are actually doing in diseased tissue. To close that gap, the team ran an integrated meta-analysis of genomic data from the 1.1 million-person cohort—all of European ancestry—and identified 125 independent genetic susceptibility loci associated with the disease. Seventeen of those loci had never been reported before.
The team then layered single-cell transcriptomic analysis on top of the genetic findings, examining gene activity at single-cell resolution in skin samples from both healthy individuals and psoriasis patients. That combination let them trace which specific cell populations are actually driving disease onset, rather than just which genes are statistically associated with it.
The single-cell data revealed a complex signaling interplay among several cell types: myeloid cells and T cells from the immune system, keratinocytes on the skin’s surface, and vascular endothelial cells lining blood vessels. These populations appear to interact in a cascade that fuels excessive inflammation. By mapping how these cell types interact across different skin layers—comparing non-lesional, lesional, and treated tissue—the researchers narrowed the field to 50 promising therapeutic target genes, each showing cell subtype-specific activity patterns.
“This research combines large-scale genomic data with precise cellular transcriptomic analysis to clearly reveal which genetic factors and cell types are involved in psoriasis pathology,” said Professor Won. “We expect our findings to serve as a key milestone in developing personalized immune-modulating treatments and new drugs tailored to individual patients.”
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