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

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 () and Baoxue Ge ()
Additional contact information
Ruijuan Zheng: Tongji University School of Medicine
Zhiqiang Li: The Affiliated Hospital of Qingdao University &The Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University
Fusheng He: BGI Genomics, BGI-Shenzhen
Haipeng Liu: Tongji University School of Medicine
Jianhua Chen: Shanghai Jiao Tong University
Jiayu Chen: Tongji University
Xuefeng Xie: BGI Genomics, BGI-Shenzhen
Juan Zhou: Shanghai Jiao Tong University
Hao Chen: Tongji University School of Medicine
Xiangyang Wu: Tongji University School of Medicine
Juehui Wu: Tongji University School of Medicine
Boyu Chen: Shanghai Jiao Tong University
Yahui Liu: Shanghai Jiao Tong University
Haiyan Cui: Tongji University School of Medicine
Lin Fan: Tongji University School of Medicine
Wei Sha: Tongji University School of Medicine
Yin Liu: Tongji University School of Medicine
Jiqiang Wang: Shanghai Jiao Tong University
Xiaochen Huang: Tongji University School of Medicine
Linfeng Zhang: Tongji University
Feifan Xu: The Sixth People’s Hospital of Nantong
Jie Wang: Tongji University School of Medicine
Yonghong Feng: Tongji University School of Medicine
Lianhua Qin: Tongji University School of Medicine
Hua Yang: Tongji University School of Medicine
Zhonghua Liu: Tongji University School of Medicine
Zhenglin Cui: Tongji University School of Medicine
Feng Liu: Tongji University School of Medicine
Xinchun Chen: Shenzhen University School of Medicine
Shaorong Gao: Tongji University
Silong Sun: BGI Genomics, BGI-Shenzhen
Yongyong Shi: The Affiliated Hospital of Qingdao University &The Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University
Baoxue Ge: Tongji University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-9

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06539-w

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