Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis

doi:10.1016/j.jid.2015.12.029

. 2016 Apr;136(4):779-787.

doi: 10.1016/j.jid.2015.12.029. Epub 2015 Dec 29.

Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis

Fusheng Zhou¹, Wenjun Wang², Changbing Shen², Hui Li², Xianbo Zuo², Xiaodong Zheng², Min Yue², Cuicui Zhang², Liang Yu², Mengyun Chen², Caihong Zhu², Xianyong Yin², Mingjun Tang², Yongjiang Li², Gang Chen², Zaixing Wang², Shengxiu Liu², Yi Zhou², Fengyu Zhang³, Weijia Zhang⁴, Caihua Li⁵, Sen Yang⁶, Liangdan Sun⁷, Xuejun Zhang⁸

Affiliations

¹ Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China.
² Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China.
³ Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA.
⁴ Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Centre for Genetic & Genomic Analysis, Genesky Biotechnologies Inc., Shanghai, China.
⁶ Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China. Electronic address: yangsen@medmail.com.cn.
⁷ Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China. Electronic address: ahmusld@163.com.
⁸ Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China. Electronic address: ayzxj@vip.sina.com.

PMID: 26743604
DOI: 10.1016/j.jid.2015.12.029

Free article

Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis

Fusheng Zhou et al. J Invest Dermatol. 2016 Apr.

Free article

. 2016 Apr;136(4):779-787.

doi: 10.1016/j.jid.2015.12.029. Epub 2015 Dec 29.

Authors

Affiliations

¹ Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China.
² Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China.
³ Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland, USA.
⁴ Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Centre for Genetic & Genomic Analysis, Genesky Biotechnologies Inc., Shanghai, China.
⁶ Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China. Electronic address: yangsen@medmail.com.cn.
⁷ Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China. Electronic address: ahmusld@163.com.
⁸ Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China; Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China; Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China. Electronic address: ayzxj@vip.sina.com.

PMID: 26743604
DOI: 10.1016/j.jid.2015.12.029

Abstract

Psoriasis is a chronic hyperproliferative and inflammatory skin disease caused by the interplay of genetic and environmental factors. DNA methylation has been linked to psoriasis, but the manner in which this process contributes to the disease is not fully understood. In this study, we carried out a three-stage epigenome-wide association study to identify disease-associated differentially methylated sites using a combination of 262 skin and 48 peripheral blood mononuclear cell samples. We not only revealed genome-wide methylation patterns for psoriasis but also identified strong associations between the skin-specific DNA methylation of nine disease-associated differentially methylated sites and psoriasis (Wilcoxon ranked PBonferroni < 0.01; methylation level difference > 0.10). Further analysis revealed that these nine disease-associated differentially methylated sites were not significantly affected by genetic variations, supporting their remarkable contributions to disease status. The expression of CYP2S1, ECE1, EIF2C2, MAN1C1, and DLGAP4 was negatively correlated with DNA methylation. These findings will help us to better understand the molecular mechanism of psoriasis.

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Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis

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Epigenome-Wide Association Analysis Identified Nine Skin DNA Methylation Loci for Psoriasis

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