title: 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.affiliation: Department of Dermatology, The Fourth Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China.|Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China.|Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China.|Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China.|Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China.|School of Basic Medical Science, Anhui Medical University, Hefei, 230032, Anhui, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China.|Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China.|Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China.
authors.forename: Changbing
authors.initials: C
authors.lastname: Shen
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China.|Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China.|Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China.
authors.forename: Songke
authors.initials: S
authors.lastname: Shen
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China.|Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China.|Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China.|Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China.|Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China.|Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China.|Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China.|Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China.|Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China. xianyongyin@gmail.com.|Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China. xianyongyin@gmail.com.|Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China. xianyongyin@gmail.com.|Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China. xianyongyin@gmail.com.|Department of Genetics, and Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27517, USA. xianyongyin@gmail.com.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Yin
mesh_terms: D019002:CD56 Antigen / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000235:genetics* / Q000473:pathology; D014018:Tissue Distribution / Q000235:genetics
chemical_list: D019002:CD56 Antigen; C522918:NCAM1 protein, human; D016328:NF-kappa B
keywords: Cell types; Pathway; Psoriasis; SNPsea; Single-nucleotide polymorphism; Tissues