Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy
Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy
复制标题
麻风病6个新易感位点的发现及多效性分析
DOI：
10.1038/ng.3212
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发表时间：
2015-03-01
期刊：
影响因子：
30.8
通讯作者：
Zhang, Furen
中科院分区：
文献类型：
--
作者：
Liu, Hong;Irwanto, Astrid;Zhang, Furen
全基因组关联研究（GWAS）已经发现了几个麻风易感基因座，并提供了有力的证据，为宿主遗传因素在分枝杆菌感染中的作用提供了生物学见解。然而，所确定的基因座只能部分解释疾病的遗传性，其他的遗传风险因素仍有待发现。我们在中国人群中对8，313例麻风患者和16，017例对照者进行了3期GWAS。在确认了所有已发表的基因座的基础上，我们发现了6个新的麻风易感基因座，并对这些基因座进行了基因排序分析，结果表明BATF 3、CCDC 88和CIITA-SOCS 1为新的麻风易感基因。一个系统的多效性的评估表明，麻风易感基因座的高度倾向，显示与自身免疫和炎症性疾病。进一步的分析表明，感染的分子传感可能在这些疾病中具有相似的致病作用，而免疫反应在感染性和炎症性疾病中具有不一致的作用。
Genome-wide association studies (GWAS) have led to the discovery of several susceptibility loci for leprosy with robust evidence, providing biological insight into the role of host genetic factors in mycobacterial infection. However, the identified loci only partially explain disease heritability, and additional genetic risk factors remain to be discovered. We performed a 3-stage GWAS of leprosy in the Chinese population using 8,313 cases and 16,017 controls. Besides confirming all previously published loci, we discovered six new susceptibility loci, and further gene prioritization analysis of these loci implicatedBATF3,CCDC88BandCIITA-SOCS1as new susceptibility genes for leprosy. A systematic evaluation of pleiotropic effects demonstrated a high tendency for leprosy susceptibility loci to show association with autoimmunity and inflammatory diseases. Further analysis suggests that molecular sensing of infection might have a similar pathogenic role across these diseases, whereas immune responses have discordant roles in infectious and inflammatory diseases.