Sequencing-based approach identified three new susceptibility loci for psoriasis

Yujun Sheng; Xin Jin; Jinhua Xu; Jinping Gao; Xiaoqing Du; Dawei Duan; Bing Li; Jinhua Zhao; Wenying Zhan; Huayang Tang; Xianfa Tang; Yang Li; Hui Cheng; Xianbo Zuo; Junpu Mei; Fusheng Zhou; Bo Liang; Gang Chen; Changbing Shen; Hongzhou Cui; Xiaoguang Zhang; Change Zhang; Wenjun Wang; Xiaodong Zheng; Xing Fan; Zaixing Wang; Fengli Xiao; Yong Cui; Yingrui Li; Jun Wang; Sen Yang; Lei Xu; Liangdan Sun; Xuejun Zhang

doi:10.1038/ncomms5331

Sequencing-based approach identified three new susceptibility loci for psoriasis

Nat Commun. 2014 Jul 9:5:4331. doi: 10.1038/ncomms5331.

Authors

Yujun Sheng¹, Xin Jin², Jinhua Xu³, Jinping Gao⁴, Xiaoqing Du⁵, Dawei Duan⁵, Bing Li⁵, Jinhua Zhao⁵, Wenying Zhan⁵, Huayang Tang⁵, Xianfa Tang⁵, Yang Li⁵, Hui Cheng⁵, Xianbo Zuo⁵, Junpu Mei⁶, Fusheng Zhou⁵, Bo Liang⁵, Gang Chen⁵, Changbing Shen⁵, Hongzhou Cui⁵, Xiaoguang Zhang⁵, Change Zhang⁵, Wenjun Wang⁵, Xiaodong Zheng⁵, Xing Fan⁵, Zaixing Wang⁵, Fengli Xiao⁵, Yong Cui⁵, Yingrui Li⁶, Jun Wang⁷, Sen Yang⁵, Lei Xu⁸, Liangdan Sun⁵, Xuejun Zhang⁹

Affiliations

¹ 1] Department of Dermatology, No. 2 Hospital, Anhui Medical University, Hefei, Anhui 230601, China [2] Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui 230022, China [3] Department of Dermatology, Huashan Hospital of Fudan University, Shanghai 200040, China [4].
² 1] BGI-Shenzhen, Shenzhen 518083, China [2] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 518055, China [3].
³ 1] Department of Dermatology, Huashan Hospital of Fudan University, Shanghai 200040, China [2].
⁴ 1] Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui 230022, China [2] Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui 230032, China [4].
⁵ 1] Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui 230022, China [2] Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui 230032, China [3] Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui 230032, China.
⁶ BGI-Shenzhen, Shenzhen 518083, China.
⁷ 1] BGI-Shenzhen, Shenzhen 518083, China [2] Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark [3] Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
⁸ Department of Computer Science and Engineering, Rm1028 Ho Sin-Hang Engineering Building, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
⁹ 1] Department of Dermatology, No. 2 Hospital, Anhui Medical University, Hefei, Anhui 230601, China [2] Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui 230022, China [3] Department of Dermatology, Huashan Hospital of Fudan University, Shanghai 200040, China [4] Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui 230032, China [5] Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui 230032, China.

PMID: 25006012
DOI: 10.1038/ncomms5331

Abstract

In a previous large-scale exome sequencing analysis for psoriasis, we discovered seven common and low-frequency missense variants within six genes with genome-wide significance. Here we describe an in-depth analysis of noncoding variants based on sequencing data (10,727 cases and 10,582 controls) with replication in an independent cohort of Han Chinese individuals consisting of 4,480 cases and 6,521 controls to identify additional psoriasis susceptibility loci. We confirmed four known psoriasis susceptibility loci (IL12B, IFIH1, ERAP1 and RNF114; 2.30 × 10(-20)≤P≤2.41 × 10(-7)) and identified three new susceptibility loci: 4q24 (NFKB1) at rs1020760 (P=2.19 × 10(-8)), 12p13.3 (CD27-LAG3) at rs758739 (P=4.08 × 10(-8)) and 17q12 (IKZF3) at rs10852936 (P=1.96 × 10(-8)). Two suggestive loci, 3p21.31 and 17q25, are also identified with P<1.00 × 10(-6). The results of this study increase the number of confirmed psoriasis risk loci and provide novel insight into the pathogenesis of psoriasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antigens, CD / genetics*
Asian People / genetics*
Case-Control Studies
China
Female
Genetic Predisposition to Disease*
Genome-Wide Association Study
Humans
Ikaros Transcription Factor / genetics*
Lymphocyte Activation Gene 3 Protein
Male
Middle Aged
NF-kappa B p50 Subunit / genetics*
Polymorphism, Single Nucleotide
Psoriasis / genetics*
Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics*
Young Adult

Substances

Antigens, CD
IKZF3 protein, human
NF-kappa B p50 Subunit
NFKB1 protein, human
Tumor Necrosis Factor Receptor Superfamily, Member 7
Ikaros Transcription Factor
Lymphocyte Activation Gene 3 Protein
Lag3 protein, human

Associated data

SRA/SRA168458