A large-scale screen for coding variants predisposing to psoriasis

Huayang Tang, Xin Jin, Yang Li, Hui Jiang, Xianfa Tang, Xu Yang, Hui Cheng, Ying Qiu, Gang Chen, Junpu Mei, Fusheng Zhou, Renhua Wu, Xianbo Zuo, Yong Zhang, Xiaodong Zheng, Qi Cai, Xianyong Yin, Cheng Quan, Haojing Shao, Yong Cui, Fangzhen Tian, Xia Zhao, Hong Liu, Fengli Xiao, Fengping Xu, Jianwen Han, Dongmei Shi, Anping Zhang, Cheng Zhou, Qibin Li, Xing Fan, Liya Lin, Hongqing Tian, Zaixing Wang, Huiling Fu, Fang Wang, Baoqi Yang, Shaowei Huang, Bo Liang, Xuefeng Xie, Yunqing Ren, Qingquan Gu, Guangdong Wen, Yulin Sun, Xueli Wu, Lin Dang, Min Xia, Junjun Shan, Tianhang Li, Lin Yang, Xiuyun Zhang, Yuzhen Li, Chundi He, Aie Xu, Liping Wei, Xiaohang Zhao, Xinghua Gao, Jinhua Xu, Furen Zhang, Jianzhong Zhang, Yingrui Li, Liangdan Sun, Jianjun Liu, Runsheng Chen, Sen Yang, Jun Wang, Xuejun Zhang

To explore the contribution of functional coding variants to psoriasis, we analyzed nonsynonymous single-nucleotide variants (SNVs) across the genome by exome sequencing in 781 psoriasis cases and 676 controls and through follow-up validation in 1,326 candidate genes by targeted sequencing in 9,946 psoriasis cases and 9,906 controls from the Chinese population. We discovered two independent missense SNVs in IL23R and GJB2 of low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. Rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association. Single-variant and gene-based association analyses of nonsynonymous SNVs did not identify newly associated genes for psoriasis in the regions subjected to targeted resequencing. This suggests that coding variants in the 1,326 targeted genes contribute only a limited fraction of the overall genetic risk for psoriasis.