Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis

Xianbo Zuo; Liangdan Sun; Xianyong Yin; Jinping Gao; Yujun Sheng; Jinhua Xu; Jianzhong Zhang; Chundi He; Ying Qiu; Guangdong Wen; Hongqing Tian; Xiaodong Zheng; Shengxiu Liu; Wenjun Wang; Weiran Li; Yuyan Cheng; Longdan Liu; Yan Chang; Zaixing Wang; Zenggang Li; Longnian Li; Jianping Wu; Ling Fang; Changbing Shen; Fusheng Zhou; Bo Liang; Gang Chen; Hui Li; Yong Cui; Aie Xu; Xueqin Yang; Fei Hao; Limin Xu; Xing Fan; Yuzhen Li; Rina Wu; Xiuli Wang; Xiaoming Liu; Min Zheng; Shunpeng Song; Bihua Ji; Hong Fang; Jianbin Yu; Yongxin Sun; Yan Hui; Furen Zhang; Rongya Yang; Sen Yang; Xuejun Zhang

doi:10.1038/ncomms7793

Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis

Nat Commun. 2015 Apr 9:6:6793. doi: 10.1038/ncomms7793.

Authors

Xianbo Zuo¹, Liangdan Sun¹, Xianyong Yin¹, Jinping Gao², Yujun Sheng², Jinhua Xu³, Jianzhong Zhang⁴, Chundi He⁵, Ying Qiu⁶, Guangdong Wen⁴, Hongqing Tian⁷, Xiaodong Zheng², Shengxiu Liu², Wenjun Wang², Weiran Li², Yuyan Cheng², Longdan Liu², Yan Chang², Zaixing Wang², Zenggang Li², Longnian Li², Jianping Wu², Ling Fang², Changbing Shen², Fusheng Zhou², Bo Liang², Gang Chen², Hui Li², Yong Cui⁸, Aie Xu⁹, Xueqin Yang¹⁰, Fei Hao¹¹, Limin Xu¹², Xing Fan², Yuzhen Li¹³, Rina Wu¹⁴, Xiuli Wang¹⁵, Xiaoming Liu¹⁶, Min Zheng¹⁷, Shunpeng Song¹⁸, Bihua Ji¹⁹, Hong Fang²⁰, Jianbin Yu²¹, Yongxin Sun²², Yan Hui²³, Furen Zhang⁷, Rongya Yang²⁴, Sen Yang², Xuejun Zhang¹

Affiliations

¹ 1] Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui 230022, China [2] Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China [3] Department of Dermatology, No.2 Hospital, Anhui Medical University, Hefei, Anhui 230022, China [4] Collaborative Innovation Center of Complex and Severe Skin Disease, Anhui Medical University, Hefei, Anhui 230032, China [5] State Key Lab Incubation of Dermatology, Ministry of Science and Technology, Hefei, Anhui 230032, China [6] Key Lab of Dermatology, Ministry of Education, Hefei, Anhui 230032, China [7] Key Lab of Gene Resources Utilization for Severe Inherited Disorders, Anhui 230032, China.
² 1] Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui 230022, China [2] Collaborative Innovation Center of Complex and Severe Skin Disease, Anhui Medical University, Hefei, Anhui 230032, China [3] State Key Lab Incubation of Dermatology, Ministry of Science and Technology, Hefei, Anhui 230032, China [4] Key Lab of Dermatology, Ministry of Education, Hefei, Anhui 230032, China [5] Key Lab of Gene Resources Utilization for Severe Inherited Disorders, Anhui 230032, China.
³ 1] Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China [2] Collaborative Innovation Center of Complex and Severe Skin Disease, Anhui Medical University, Hefei, Anhui 230032, China.
⁴ Department of Dermatology, Peking University People's Hospital, Beijing 100044, China.
⁵ Department of Dermatology, No.1 Hospital of China Medical University, Shenyang, Liaoning 110001, China.
⁶ Department of Dermatology, Jining No. 1 People's Hospital, Jining, Shandong 272011, China.
⁷ Shandong Provincial Institute of Dermatology and Venereology, Jinan, Shandong 250022, China.
⁸ 1] Collaborative Innovation Center of Complex and Severe Skin Disease, Anhui Medical University, Hefei, Anhui 230032, China [2] State Key Lab Incubation of Dermatology, Ministry of Science and Technology, Hefei, Anhui 230032, China [3] Key Lab of Dermatology, Ministry of Education, Hefei, Anhui 230032, China [4] Key Lab of Gene Resources Utilization for Severe Inherited Disorders, Anhui 230032, China.
⁹ The Third People's Hospital of Hangzhou, Hangzhou, Zhejiang 310009, China.
¹⁰ Department of Dermatology, General Hospital of PLA Air Force, Beijing 100036, China.
¹¹ Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
¹² Department of Dermatology, Tianjin Changzheng Hospital, Tianjin 300106, China.
¹³ Department of Dermatology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China.
¹⁴ Department of Dermatology, The Affiliated Hospital of Inner Mongolia Medical College, Huhehot, Inner Mongolia 010050, China.
¹⁵ Shanghai Skin Diseases and STD Hospital, Shanghai 200050, China.
¹⁶ Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.
¹⁷ Department of Dermatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhenjiang 310009, China.
¹⁸ Department of Dermatology, Dalian Dermatosis Hosptial, Liaoning 116011, China.
¹⁹ Department of Dermatology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241000, China.
²⁰ Department of Dermatology, The First Affiliated Hospital of Zhejiang University School of Medicine, Zhenjiang 310006, China.
²¹ Department of Dermatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
²² Department of Dermatology, Anshan Tanggangzi hosptial, Liaoning 210300, China.
²³ Department of Dermatology, First Affiliated Hospital of Xinjiang Medical University, Xinjiang 830054, China.
²⁴ Department of Dermatology, General Hospital of Beijing Military Command, Beijing 100010, China.

Abstract

Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5.00 × 10(-08)). In addition, we also replicate four known susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D-LCE3E. These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis.

Publication types

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

MeSH terms

Adaptor Proteins, Vesicular Transport / genetics
Adolescent
Adult
Asian People / genetics*
Case-Control Studies
Cornified Envelope Proline-Rich Proteins / genetics
DNA-Binding Proteins / genetics
Exome / genetics
Female
Genetic Predisposition to Disease
Humans
I-kappa B Proteins / genetics
Interleukin-1 Receptor-Like 1 Protein
Interleukin-12 Subunit p40 / genetics
Intracellular Signaling Peptides and Proteins / genetics
Male
Membrane Proteins / genetics
Methylenetetrahydrofolate Reductase (NADPH2) / genetics
Microfilament Proteins / genetics
Middle Aged
Minor Histocompatibility Antigens
NF-KappaB Inhibitor alpha
Nerve Tissue Proteins / genetics
Nuclear Proteins / genetics
Polymorphism, Single Nucleotide
Psoriasis / genetics*
Receptors, Calcium-Sensing / genetics
Receptors, Cell Surface / genetics
Receptors, Interferon / genetics
Serine Endopeptidases / genetics
Trans-Activators / genetics
Young Adult

Substances

AIM2 protein, human
AP5B1 protein, human
Adaptor Proteins, Vesicular Transport
CASR protein, human
Cornified Envelope Proline-Rich Proteins
DNA-Binding Proteins
I-kappa B Proteins
IFNGR2 protein, human
IL12B protein, human
IL1RL1 protein, human
Interleukin-1 Receptor-Like 1 Protein
Interleukin-12 Subunit p40
Intracellular Signaling Peptides and Proteins
LCE3D protein, human
Membrane Proteins
Microfilament Proteins
Minor Histocompatibility Antigens
NFKBIA protein, human
Nerve Tissue Proteins
Nuclear Proteins
Receptors, Calcium-Sensing
Receptors, Cell Surface
Receptors, Interferon
SON protein, human
SYNE2 protein, human
TMC6 protein, human
TNIP1 protein, human
Trans-Activators
ZNF143 protein, human
NF-KappaB Inhibitor alpha
MTHFR protein, human
Methylenetetrahydrofolate Reductase (NADPH2)
ZFYVE16 protein, human
Serine Endopeptidases