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发现六个新的麻风病易感性基因座,并分析其在麻风病中的多效性影响。

Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy.

机构信息

1] Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, China. [2] Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, China. [3] School of Medicine, Shandong University, Jinan, China. [4] Shandong Provincial Key Laboratory for Dermatovenereology, Jinan, China.

1] Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research of Singapore, Singapore. [2] Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

出版信息

Nat Genet. 2015 Mar;47(3):267-71. doi: 10.1038/ng.3212. Epub 2015 Feb 2.

Abstract

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 implicated BATF3, CCDC88B and CIITA-SOCS1 as 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.

摘要

全基因组关联研究(GWAS)发现了几个具有确凿证据的麻风病易感基因座,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,已鉴定的基因座仅部分解释了疾病的遗传性,还需要发现其他遗传风险因素。我们在中国人群中进行了麻风病的 3 期 GWAS 研究,共纳入 8313 例病例和 16017 例对照。除了确认所有先前发表的基因座外,我们还发现了六个新的易感基因座,进一步对这些基因座的基因优先级分析表明,BATF3、CCDC88B 和 CIITA-SOCS1 是麻风病的新易感基因。对多效性效应的系统评估表明,麻风病易感基因座与自身免疫和炎症性疾病相关联的趋势很高。进一步的分析表明,感染的分子感知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同的作用。

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