Discovery of susceptibility loci associated with tuberculosis in Han Chinese
Discovery of susceptibility loci associated with tuberculosis in Han Chinese
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汉族人群结核病易感位点的发现
DOI：
10.1093/hmg/ddx365
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发表时间：
2017-12-01
影响因子：
3.5
通讯作者：
Shen, A-Dong
中科院分区：
文献类型：
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作者：
Qi, Hui;Zhang, Yong-Biao;Shen, A-Dong
全基因组关联研究（GWAS）揭示了结核病（TB）易感性遗传因素的全球异质性。尽管中国的结核病负担位居全球第三，但尚未进行过结核病相关的GWAS。在这里，我们在中国汉族人群中对结核病进行了第一个三阶段GWAS。在第1阶段（发现阶段），经过质量控制，保留了972名TB患者和1537名对照中存在的691 388个SNP。在对另外3460名结核病患者和4862名对照（2期和3期）进行重复研究后，我们确定了3个与结核病相关的显著位点，其中最显著的是rs 4240897（logistic回归P = 1.41 × 10-11，比值比= 0.79）。上述3个SNP分别存在于MFN 2、RGS 12和人类白细胞抗原II类β链基因编码区，均为结核病相关的候选免疫基因。我们的发现为中国汉族人群结核病的遗传背景提供了新的见解。
Genome-wide association studies (GWASs) have revealed the worldwide heterogeneity of genetic factors in tuberculosis (TB) susceptibility. Despite having the third highest global TB burden, no TB-related GWAS has been performed in China. Here, we performed the first three-stage GWAS on TB in the Han Chinese population. In the stage 1 (discovery stage), after quality control, 691 388 SNPs present in 972 TB patients and 1537 controls were retained. After replication on an additional 3460 TB patients and 4862 controls (stages 2 and 3), we identified three significant loci associated with TB, the most significant of which was rs4240897 (logistic regression P = 1.41 × 10-11, odds ratio = 0.79). The aforementioned three SNPs were harbored by MFN2, RGS12 and human leukocyte antigen class II beta chain paralogue encoding genes, all of which are candidate immune genes associated with TB. Our findings provide new insight into the genetic background of TB in the Han Chinese population.