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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.

SUBMITTER: Zuo X 

PROVIDER: S-EPMC4403312 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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

Zuo Xianbo X   Sun Liangdan L   Yin Xianyong X   Gao Jinping J   Sheng Yujun Y   Xu Jinhua J   Zhang Jianzhong J   He Chundi C   Qiu Ying Y   Wen Guangdong G   Tian Hongqing H   Zheng Xiaodong X   Liu Shengxiu S   Wang Wenjun W   Li Weiran W   Cheng Yuyan Y   Liu Longdan L   Chang Yan Y   Wang Zaixing Z   Li Zenggang Z   Li Longnian L   Wu Jianping J   Fang Ling L   Shen Changbing C   Zhou Fusheng F   Liang Bo B   Chen Gang G   Li Hui H   Cui Yong Y   Xu Aie A   Yang Xueqin X   Hao Fei F   Xu Limin L   Fan Xing X   Li Yuzhen Y   Wu Rina R   Wang Xiuli X   Liu Xiaoming X   Zheng Min M   Song Shunpeng S   Ji Bihua B   Fang Hong H   Yu Jianbin J   Sun Yongxin Y   Hui Yan Y   Zhang Furen F   Yang Rongya R   Yang Sen S   Zhang Xuejun X  

Nature communications 20150409

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,  ...[more]

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