Genomics of human pulmonary tuberculosis: from genes to pathways.
Genomics of human pulmonary tuberculosis: from genes to pathways.
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DOI：
10.1007/s40142-017-0130-9
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发表时间：
2017-12
影响因子：
2.1
通讯作者：
Williams SM
中科院分区：
文献类型：
--
作者：
Stein CM;Sausville L;Wejse C;Sobota RS;Zetola NM;Hill PC;Boom WH;Scott WK;Sirugo G;Williams SM
结核病 (TB) 由结核分枝杆菌 (MTB) 引起，仍然是全球主要的公共卫生威胁。多项证据支持宿主遗传因素在结核病和结核分枝杆菌感染的抵抗/易感性中的作用。然而，候选基因和全基因组关联研究（GWAS）的结果在很大程度上不一致，因此尚未出现潜在结核病风险的内聚遗传模型。尽管很难确定一致的遗传关联，但结核病和结核分枝杆菌感染的遗传研究已经揭示了一些有据可查的基因座。本综述介绍了这些经过充分验证的基因，但在如何将这些基因转化为更好地了解结核病方面仍然存在很大差距。为了解决这个问题，我们提出了一种基于路径的标准关联分析扩展，用来自候选基因和 GWAS 研究的最佳验证基因播种结果。使用通路分析显着丰富了一些通路，这可能有助于解释结核病风险的人群模式。总之，我们主张采用新方法来研究结核病宿主遗传分析，以扩展传统的关联方法。
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a major public health threat globally. Several lines of evidence support a role for host genetic factors in resistance/susceptibility to TB disease and MTB infection. However, results across candidate gene and genome-wide association studies (GWAS) are largely inconsistent, so a cohesive genetic model underlying TB risk has not emerged. Despite the difficulties in identifying consistent genetic associations, genetic studies of TB and MTB infection have revealed a few well-documented loci. These well validated genes are presented in this review, but there remains a large gap in how these genes translate into better understanding of TB. To address this, we present a pathway based extension of standard association analyses, seeding the results with the best validated genes from candidate gene and GWAS studies. Several pathways were significantly enriched using pathway analyses that may help to explain population patterns of TB risk. In conclusion, we advocate for novel approaches to the study of host genetic analysis of TB that extend traditional association approaches.