Sequencing-based approach identified three new susceptibility loci for psoriasis
Sequencing-based approach identified three new susceptibility loci for psoriasis
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基于测序的方法确定了银屑病的三个新易感位点
DOI：
10.1038/ncomms5331
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发表时间：
2014-07-01
影响因子：
16.6
通讯作者：
Zhang, Xuejun
中科院分区：
文献类型：
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作者：
Sheng, Yujun;Jin, Xin;Zhang, Xuejun
在之前的一项针对银屑病的大规模外显子组测序分析中，我们在6个基因中发现了7个具有全基因组意义的常见和低频错义变体。在此，我们描述了一项基于测序数据（10，727例病例和10，582例对照）的非编码变异的深入分析，并在一个由4，480例病例和6，521例对照组成的独立汉族个体队列中进行复制，以确定其他银屑病易感基因座。我们证实了四个已知的银屑病易感基因位点（IL 12 B，IFIH 1，ERAP 1和RNF 114; 2.30 × 10−20≤P≤2.41 × 10−7），并确定了三个新的易感基因座：4 q24（NFKB 1）位于rs 1020760（P=2.19 × 10−8），12p13.3（CD 27-LAG 3）位于rs758739（P=4.08 × 10−8），17 q12（IKZF 3）位于rs 10852936（P=1.96 × 10−8）。两个提示性位点3p21.31和17 q25也被确定，P <1.00 × 10−6。这项研究的结果增加了确认的银屑病风险位点的数量，并为银屑病的发病机制提供了新的见解。
In a previous large-scale exome sequencing analysis for psoriasis, we discovered seven common and low-frequency missense variants within six genes with genome-wide significance. Here we describe an in-depth analysis of noncoding variants based on sequencing data (10,727 cases and 10,582 controls) with replication in an independent cohort of Han Chinese individuals consisting of 4,480 cases and 6,521 controls to identify additional psoriasis susceptibility loci. We confirmed four known psoriasis susceptibility loci (IL12B,IFIH1,ERAP1andRNF114; 2.30 × 10−20≤P≤2.41 × 10−7) and identified three new susceptibility loci: 4q24 (NFKB1) at rs1020760 (P=2.19 × 10−8), 12p13.3 (CD27-LAG3) at rs758739 (P=4.08 × 10−8) and 17q12 (IKZF3) at rs10852936 (P=1.96 × 10−8). Two suggestive loci, 3p21.31 and 17q25, are also identified withP<1.00 × 10−6. The results of this study increase the number of confirmed psoriasis risk loci and provide novel insight into the pathogenesis of psoriasis.