1] Department of Dermatology, No. 2 Hospital, Anhui Medical University, Hefei, Anhui 230601, China [2] Institute of Dermatology and Department of Dermatology, No. 1 Hospital, Anhui Medical University, Hefei, Anhui 230022, China [3] Department of Dermatology, Huashan Hospital of Fudan University, Shanghai 200040, China [4].
1] BGI-Shenzhen, Shenzhen 518083, China [2] School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 518055, China [3].
Nat Commun. 2014 Jul 9;5:4331. doi: 10.1038/ncomms5331.
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, ERAP1 and RNF114; 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 with P<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.
在之前一项针对银屑病的大规模外显子测序分析中，我们在六个基因中发现了七个具有全基因组意义的常见和低频错义变异。在这里，我们描述了基于测序数据（10727 例病例和 10582 例对照）对非编码变异的深入分析，并在一个由 4480 例病例和 6521 例对照组成的汉族独立队列中进行了复制，以确定其他银屑病易感基因座。我们确认了四个已知的银屑病易感基因座（IL12B、IFIH1、ERAP1 和 RNF114；2.30×10(-20)≤P≤2.41×10(-7))，并鉴定了三个新的易感基因座：4q24（NFKB1）上的 rs1020760（P=2.19×10(-8))，12p13.3（CD27-LAG3）上的 rs758739（P=4.08×10(-8))和 17q12（IKZF3）上的 rs10852936（P=1.96×10(-8))。两个提示性基因座 3p21.31 和 17q25 也被确定为 P<1.00×10(-6)。这项研究的结果增加了已确认的银屑病风险基因座的数量，并为银屑病的发病机制提供了新的见解。
