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

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

Author information

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.

PMID:
25854761
PMCID:
PMC4403312
DOI:
10.1038/ncomms7793
[Indexed for MEDLINE]
Free PMC Article

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