Genetic Study on Small Insertions and Deletions in Psoriasis Reveals a Role in Complex Human Diseases
Genetic Study on Small Insertions and Deletions in Psoriasis Reveals a Role in Complex Human Diseases
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银屑病中小插入和缺失的遗传学研究揭示了其在复杂人类疾病中的作用
DOI：
10.1016/j.jid.2019.03.1157
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发表时间：
2019
影响因子：
6.5
通讯作者：
Gao Qia
中科院分区：
文献类型：
--
作者：
Zhen Qi;Yang Zhenjun;Wang Wenjun;Li Bao;Bai Mingzhou;Wu Jing;Ge Huiyao;Dong Zirui;Shen Juan;Tang Huayang;Sun Silong;Qiu Ying;Xu Jinjin;Qu Xiaoxiao;Wang Ying;Yi Meihui;Hu Huaqing;Xu Yuanhong;Cheng Hui;Liang Bo;Gao Jinping;Shao Haojing;Jian Zhengwen;Gao Qia
基于单核苷酸多态性的遗传研究为复杂疾病的遗传结构提供了有价值的见解。然而，大多数这些疾病的大部分遗传能力仍然无法解释，并且小插入和缺失（InDels）的影响一直被忽视。我们使用SOAP-PopIndel方法对32,043名中国汉人的1,326个基因的indel外显子组序列数据进行了全面筛选，并在25个与银屑病相关的易感基因中鉴定出29个未报道的indel。具体来说，我们确定了12个常见、9个低频和8个罕见的InDels，这些InDels解释了牛皮癣遗传率的1.29%。进一步分析发现kiaa0319、RELN、NCAPG、ABO、AADACL2、LMAN1、FLG、HERC5、CCDC66、LEKR1、AFF3、ABCG2、ANXA7、SYTL2、GIPR、METTL1和fyco1是牛皮癣未报道的基因。此外，鉴定出的indel与以下已报道的基因相关：IFIH1、ERAP1、ERAP2、LNPEP、UBLCP1和stat3；在jb2和znf816a中发现了未报道的外显子indel的独立关联。我们的研究丰富了牛皮癣的遗传基础和发病机制，突出了InDels对复杂人类疾病不可忽视的影响。
Genetic studies based on single-nucleotide polymorphisms have provided valuable insights into the genetic architecture of complex diseases. However, a large fraction of heritability for most of these diseases remains unexplained, and the impact of small insertions and deletions (InDels) has been neglected. We performed a comprehensive screen on the exome sequence data of 1,326 genes using the SOAP-PopIndel method for InDels in 32,043 Chinese Han individuals and identified 29 unreported InDels within 25 susceptibility genes associated with psoriasis. Specifically, we identified 12 common, 9 low-frequency, and 8 rare InDels that explained approximately 1.29% of the heritability of psoriasis. Further analyses identifiedKIAA0319, RELN, NCAPG, ABO, AADACL2,LMAN1,FLG,HERC5,CCDC66,LEKR1, AFF3, ABCG2, ANXA7, SYTL2,GIPR, METTL1,andFYCO1as unreported genes for psoriasis. In addition, identified InDels were associated with the following reported genes:IFIH1, ERAP1, ERAP2, LNPEP, UBLCP1,andSTAT3;unreported independent associations for exonic InDels were found withinGJB2andZNF816A. Our study enriched the genetic basis and pathogenesis of psoriasis and highlighted the non-negligible impact of InDels on complex human diseases.