A large-scale screen for coding variants predisposing to psoriasis

作者：Tang Huayang; Jin Xin; Li Yang; Jiang Hui; Tang Xianfa; Yang Xu; Cheng Hui; Qiu Ying; Chen Gang; Mei Junpu; Zhou Fusheng; Wu Renhua; Zuo Xianbo; Zhang Yong; Zheng Xiaodong; Cai Qi; Yin Xianyong; Quan Cheng; Shao Haojing; Cui Yong; Tian Fangzhen; Zhao Xia; Liu Hong; Xiao Fengli; Xu Fengping; Han Jianwen; Shi Dongmei; Zhang Anping; Zhou Cheng; Li Qibin; Fan Xing; Lin Liya; Tian Hongqing; Wang Zaixing; Fu Huiling; Wang Fang; Yang Baoqi; Huang Shaowei

来源：Nature Genetics, 2014, 46(1): 45.

DOI：10.1038/ng.2827

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.

• 单位
  安徽医科大学; 中国科学院生物物理研究所; 哈尔滨医科大学; 中国医学科学院北京协和医院; 山东省医学科学院; 深圳华大基因研究院; 中国医科大学; 北京大学; 2; 复旦大学; 中国人民解放军海军总医院; 华南理工大学; 内蒙古医学院; 1