Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese.

Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese.

Nature communications (2018-10-06)

Ruijuan Zheng, Zhiqiang Li, Fusheng He, Haipeng Liu, Jianhua Chen, Jiayu Chen, Xuefeng Xie, Juan Zhou, Hao Chen, Xiangyang Wu, Juehui Wu, Boyu Chen, Yahui Liu, Haiyan Cui, Lin Fan, Wei Sha, Yin Liu, Jiqiang Wang, Xiaochen Huang, Linfeng Zhang, Feifan Xu, Jie Wang, Yonghong Feng, Lianhua Qin, Hua Yang, Zhonghua Liu, Zhenglin Cui, Feng Liu, Xinchun Chen, Shaorong Gao, Silong Sun, Yongyong Shi, Baoxue Ge

PMID30287856

ABSTRACT

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), and remains a leading public health problem. Previous studies have identified host genetic factors that contribute to Mtb infection outcomes. However, much of the heritability in TB remains unaccounted for and additional susceptibility loci most likely exist. We perform a multistage genome-wide association study on 2949 pulmonary TB patients and 5090 healthy controls (833 cases and 1220 controls were genome-wide genotyped) from Han Chinese population. We discover two risk loci: 14q24.3 (rs12437118, Pcombined = 1.72 × 10-11, OR = 1.277, ESRRB) and 20p13 (rs6114027, Pcombined = 2.37 × 10-11, OR = 1.339, TGM6). Moreover, we determine that the rs6114027 risk allele is related to decreased TGM6 transcripts in PBMCs from pulmonary TB patients and severer pulmonary TB disease. Furthermore, we find that tgm6-deficient mice are more susceptible to Mtb infection. Our results provide new insights into the genetic etiology of TB.