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

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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.

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Acknowledgments

The authors thank all participants in this study. We appreciate the kind help from Dr. Kamil Slowikowski at Broad Institute, Boston, USA and Yuanshen Huang at University of British Columbia, Canada.

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Authors and Affiliations

  1. Department of Dermatology, The Fourth Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China

    Yan Lin

  2. Institute of Dermatology, Department of Dermatology, The First Affiliated Hospital, Anhui Medical University, Hefei, 230032, Anhui, China

    Yan Lin, Changbing Shen, Songke Shen, Xiaodong Zheng, Xianbo Zuo, Sen Yang, Xuejun Zhang & Xianyong Yin

  3. Key Lab of Dermatology, Ministry of Education (Anhui Medical University) and State Key Lab of Dermatology Incubation, Hefei, 230032, Anhui, China

    Yan Lin, Pan Zhao, Changbing Shen, Songke Shen, Xiaodong Zheng, Xianbo Zuo, Sen Yang, Xuejun Zhang & Xianyong Yin

  4. Key Lab of Gene Resource Utilization for Complex Diseases, Hefei, 230032, Anhui, China

    Yan Lin, Pan Zhao, Changbing Shen, Songke Shen, Xiaodong Zheng, Xianbo Zuo, Sen Yang, Xuejun Zhang & Xianyong Yin

  5. Collaborative Innovation Center for Complex and Severe Dermatosis, Anhui Medical University, Hefei, 230032, Anhui, China

    Yan Lin, Pan Zhao, Changbing Shen, Songke Shen, Xiaodong Zheng, Xianbo Zuo, Sen Yang, Xuejun Zhang & Xianyong Yin

  6. School of Basic Medical Science, Anhui Medical University, Hefei, 230032, Anhui, China

    Pan Zhao

  7. Department of Genetics, and Renaissance Computing Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27517, USA

    Xianyong Yin

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  1. Yan Lin
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  2. Pan Zhao
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  3. Changbing Shen
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  4. Songke Shen
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  5. Xiaodong Zheng
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  6. Xianbo Zuo
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  7. Sen Yang
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  8. Xuejun Zhang
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  9. Xianyong Yin
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Corresponding author

Correspondence to Xianyong Yin.

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The authors declare that they have no conflict of interest.

Funding

This study was funded by Normal Project (81370044), Youth Project (81000692), key Project of National Natural Science Foundation of China (81130031), Anhui High Education Youth Talent Fund (2014, X. Yin) and Anhui Medical University Doctoral Fund (XJ201429).

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board of Institute of Dermatology, Anhui Medical University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

Additional information

Communicated by S. Hohmann.

Yan Lin and Pan Zhao share the first authorship.

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Lin, Y., Zhao, P., Shen, C. et al. Identification of cell types, tissues and pathways affected by risk loci in psoriasis. Mol Genet Genomics 291, 1005–1012 (2016). https://doi.org/10.1007/s00438-015-1141-4

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