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

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...

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Detalles Bibliográficos
Autores principales: Zuo, Xianbo, Sun, Liangdan, Yin, Xianyong, Gao, Jinping, Sheng, Yujun, Xu, Jinhua, Zhang, Jianzhong, He, Chundi, Qiu, Ying, Wen, Guangdong, Tian, Hongqing, Zheng, Xiaodong, Liu, Shengxiu, Wang, Wenjun, Li, Weiran, Cheng, Yuyan, Liu, Longdan, Chang, Yan, Wang, Zaixing, Li, Zenggang, Li, Longnian, Wu, Jianping, Fang, Ling, Shen, Changbing, Zhou, Fusheng, Liang, Bo, Chen, Gang, Li, Hui, Cui, Yong, Xu, Aie, Yang, Xueqin, Hao, Fei, Xu, Limin, Fan, Xing, Li, Yuzhen, Wu, Rina, Wang, Xiuli, Liu, Xiaoming, Zheng, Min, Song, Shunpeng, Ji, Bihua, Fang, Hong, Yu, Jianbin, Sun, Yongxin, Hui, Yan, Zhang, Furen, Yang, Rongya, Yang, Sen, Zhang, Xuejun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403312/
https://www.ncbi.nlm.nih.gov/pubmed/25854761
http://dx.doi.org/10.1038/ncomms7793
Descripción
Sumario: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.

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