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

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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 6793 (Apr 09 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 25854761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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