汉族人群结核病易感性相关位点的发现。

Discovery of susceptibility loci associated with tuberculosis in Han Chinese.

机构信息

Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, Key Laboratory of Major Diseases in Children, Ministry of Education, National Clinical Research Center for Respiratory Diseases, National Key Discipline of Pediatrics (Capital Medical University), Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

Chinese Academy of Sciences and Key Laboratory of Genome Science and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

Hum Mol Genet. 2017 Dec 1;26(23):4752-4763. doi: 10.1093/hmg/ddx365.

DOI:10.1093/hmg/ddx365

PMID:29036319

Abstract

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.

摘要

全基因组关联研究（GWAS）揭示了结核病（TB）易感性的遗传因素在全球范围内存在异质性。尽管中国的全球结核病负担位居第三，但尚未进行任何与结核病相关的 GWAS。在这里，我们对汉族人群中的结核病进行了首次三阶段 GWAS。在第一阶段（发现阶段），经过质量控制后，保留了 972 例结核病患者和 1537 例对照者中存在的 691388 个 SNP。在对另外 3460 例结核病患者和 4862 例对照者（第 2 阶段和第 3 阶段）进行复制后，我们确定了三个与结核病相关的显著位点，其中最显著的是 rs4240897（逻辑回归 P = 1.41×10-11，优势比 = 0.79）。上述三个 SNP 位于 MFN2、RGS12 和人类白细胞抗原 II 类β链编码基因的同源基因中，这些基因都是与结核病相关的候选免疫基因。我们的研究结果为汉族人群中结核病的遗传背景提供了新的见解。