Identification of cell types, tissues and pathways affected by risk loci in psoriasis.

Abstract

Many common variants have been found associated with the risk of psoriasis, but the underlying mechanism is still largely unknown, mostly owing to the difficulty in dissecting the mechanism of each variant using representative cell type and tissue in biological experiments. We applied an integrative method SNPsea which has been developed by investigators in Broad, to identify the most relevant cell types, tissues, and pathways to psoriasis by assessing the condition specificity affected by psoriasis genome-wide association studies-implicated genes. We employed this software on 89 single-nucleotide polymorphisms with genome-wide significance in Han Chinese and Caucasian populations. We found significant evidence for peripheral blood CD56 + NK cells (P = 1.30 × 10(-7)), Langerhans cells (P = 4.96 × 10(-6)) and CD14+ monocytes (P < 4.80 × 10(-5)) in psoriasis. We suggested that the DNase I hypersensitivity sites in CD14+ cells were active in psoriasis (P = 2.20 × 10(-16)). In addition, we discovered that biotic stimulus response, cytokine production and NF-κB pathways were significantly activated in psoriasis (P < 1.00 × 10(-5)). In conclusion, we found several innate immune cells and immune pathways in psoriasis that will help guide biological experiments for psoriasis risk variants in future.

• Authors: Yan Lin, Pan Zhao, Changbing Shen, Songke Shen, Xiaodong Zheng, Xianbo Zuo, Sen Yang, Xuejun Zhang, Xianyong Yin
• Journal: Molecular genetics and genomics : MGG (Mol Genet Genomics) Vol. 291 Issue 2 Pg. 1005-12 (Apr 2016) ISSN: 1617-4623 [Electronic] Germany
• PMID: 26563434 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD56 Antigen
• NCAM1 protein, human
• NF-kappa B

Topics

• CD56 Antigen (genetics)
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Humans
• Immunity, Innate (genetics)
• Killer Cells, Natural (metabolism, pathology)
• Metabolic Networks and Pathways (genetics)
• Monocytes (metabolism, pathology)
• NF-kappa B (biosynthesis, genetics)
• Polymorphism, Single Nucleotide
• Psoriasis (genetics, pathology)
• Tissue Distribution (genetics)