Genome‐wide association study of tuberculosis in the western Chinese Han and Tibetan population

Abstract Tuberculosis (TB) remains a serious global public health threat. Accumulated evidence has demonstrated that human susceptibility to TB has a strong genetic basis. And different susceptibility single nucleotide polymorphisms (SNP) have been reported in different studies. To gain greater insi...

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Main Authors: Hao Bai, Mengyuan Song, Shikun Lei, Lin Jiao, Xuejiao Hu, Tao Wu, Jiajia Song, Tangyuheng Liu, Wu Peng, Zhenzhen Zhao, Zirui Meng, Binwu Ying
Format: Article
Language:English
Published: Wiley 2023-04-01
Series:MedComm
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Online Access:https://doi.org/10.1002/mco2.250
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author Hao Bai
Mengyuan Song
Shikun Lei
Lin Jiao
Xuejiao Hu
Tao Wu
Jiajia Song
Tangyuheng Liu
Wu Peng
Zhenzhen Zhao
Zirui Meng
Binwu Ying
author_facet Hao Bai
Mengyuan Song
Shikun Lei
Lin Jiao
Xuejiao Hu
Tao Wu
Jiajia Song
Tangyuheng Liu
Wu Peng
Zhenzhen Zhao
Zirui Meng
Binwu Ying
author_sort Hao Bai
collection DOAJ
description Abstract Tuberculosis (TB) remains a serious global public health threat. Accumulated evidence has demonstrated that human susceptibility to TB has a strong genetic basis. And different susceptibility single nucleotide polymorphisms (SNP) have been reported in different studies. To gain greater insight into the host susceptibility to TB, we perform a two‐stage genome‐wide association study to identify the susceptible loci of TB. In the discovery stage, 3116 (1532 TB patients and 1584 healthy controls) and 439 (211 TB patients and 228 healthy controls) individuals were genome‐wide genotyped from a western Chinese Han and Tibetan population, respectively. Based on the additive genetic model, we discovered 14 and three independent loci that had potential associations with TB susceptibility in the Chinese Han and Tibetan populations, respectively (p < 1 × 10−5). Furthermore, we conducted an imputation‐based meta‐analysis on another two East Asia cohorts to replicate our findings. We identified one independent locus harbored by the human leukocyte antigen (HLA) class II genes that was genome‐wide significantly associated with TB (lead SNP rs111875628 with a p‐value of 2.20 × 10−9). Our findings suggest a novel mechanism of the interaction with the HLA class II genes and reinforce the importance of the HLA class II alleles in response to TB.
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spelling doaj-art-634f50afb18e4f11a2710c850a86eb3f2025-01-24T05:36:29ZengWileyMedComm2688-26632023-04-0142n/an/a10.1002/mco2.250Genome‐wide association study of tuberculosis in the western Chinese Han and Tibetan populationHao Bai0Mengyuan Song1Shikun Lei2Lin Jiao3Xuejiao Hu4Tao Wu5Jiajia Song6Tangyuheng Liu7Wu Peng8Zhenzhen Zhao9Zirui Meng10Binwu Ying11Department of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaDepartment of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu P. R. ChinaDepartment of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaDivision of Laboratory Medicine Guangdong Provincial People's Hospital Guangdong Academy of Medical Sciences Guangzhou P. R. ChinaDepartment of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaDepartment of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaDepartment of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaDepartment of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaDepartment of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaDepartment of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaDepartment of Laboratory Medicine West China Hospital Sichuan University Chengdu P. R. ChinaAbstract Tuberculosis (TB) remains a serious global public health threat. Accumulated evidence has demonstrated that human susceptibility to TB has a strong genetic basis. And different susceptibility single nucleotide polymorphisms (SNP) have been reported in different studies. To gain greater insight into the host susceptibility to TB, we perform a two‐stage genome‐wide association study to identify the susceptible loci of TB. In the discovery stage, 3116 (1532 TB patients and 1584 healthy controls) and 439 (211 TB patients and 228 healthy controls) individuals were genome‐wide genotyped from a western Chinese Han and Tibetan population, respectively. Based on the additive genetic model, we discovered 14 and three independent loci that had potential associations with TB susceptibility in the Chinese Han and Tibetan populations, respectively (p < 1 × 10−5). Furthermore, we conducted an imputation‐based meta‐analysis on another two East Asia cohorts to replicate our findings. We identified one independent locus harbored by the human leukocyte antigen (HLA) class II genes that was genome‐wide significantly associated with TB (lead SNP rs111875628 with a p‐value of 2.20 × 10−9). Our findings suggest a novel mechanism of the interaction with the HLA class II genes and reinforce the importance of the HLA class II alleles in response to TB.https://doi.org/10.1002/mco2.250genome‐wide association studyhuman leukocyte antigensusceptibilitytuberculosis
spellingShingle Hao Bai
Mengyuan Song
Shikun Lei
Lin Jiao
Xuejiao Hu
Tao Wu
Jiajia Song
Tangyuheng Liu
Wu Peng
Zhenzhen Zhao
Zirui Meng
Binwu Ying
Genome‐wide association study of tuberculosis in the western Chinese Han and Tibetan population
MedComm
genome‐wide association study
human leukocyte antigen
susceptibility
tuberculosis
title Genome‐wide association study of tuberculosis in the western Chinese Han and Tibetan population
title_full Genome‐wide association study of tuberculosis in the western Chinese Han and Tibetan population
title_fullStr Genome‐wide association study of tuberculosis in the western Chinese Han and Tibetan population
title_full_unstemmed Genome‐wide association study of tuberculosis in the western Chinese Han and Tibetan population
title_short Genome‐wide association study of tuberculosis in the western Chinese Han and Tibetan population
title_sort genome wide association study of tuberculosis in the western chinese han and tibetan population
topic genome‐wide association study
human leukocyte antigen
susceptibility
tuberculosis
url https://doi.org/10.1002/mco2.250
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