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

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 add...

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Detalles Bibliográficos
Autores principales: Zheng, Ruijuan, Li, Zhiqiang, He, Fusheng, Liu, Haipeng, Chen, Jianhua, Chen, Jiayu, Xie, Xuefeng, Zhou, Juan, Chen, Hao, Wu, Xiangyang, Wu, Juehui, Chen, Boyu, Liu, Yahui, Cui, Haiyan, Fan, Lin, Sha, Wei, Liu, Yin, Wang, Jiqiang, Huang, Xiaochen, Zhang, Linfeng, Xu, Feifan, Wang, Jie, Feng, Yonghong, Qin, Lianhua, Yang, Hua, Liu, Zhonghua, Cui, Zhenglin, Liu, Feng, Chen, Xinchun, Gao, Shaorong, Sun, Silong, Shi, Yongyong, Ge, Baoxue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172286/
https://www.ncbi.nlm.nih.gov/pubmed/30287856
http://dx.doi.org/10.1038/s41467-018-06539-w
Descripción
Sumario: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, P(combined) = 1.72 × 10(−11), OR = 1.277, ESRRB) and 20p13 (rs6114027, P(combined) = 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.

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