A next generation sequencing combined genome-wide association study identifies novel tuberculosis susceptibility loci in Chinese population

Mo Li; Yi Hu; Baihui Zhao; Luan Chen; Hailiang Huang; Cong Huai; Xiaoqing Zhang; Jinghong Zhang; Wei Zhou; Lu Shen; Qi Zhen; Bao Li; Wenjun Wang; Lin He; Shengying Qin

doi:10.1016/j.ygeno.2021.05.035

A next generation sequencing combined genome-wide association study identifies novel tuberculosis susceptibility loci in Chinese population

Genomics. 2021 Jul;113(4):2377-2384. doi: 10.1016/j.ygeno.2021.05.035. Epub 2021 May 28.

Authors

Mo Li¹, Yi Hu², Baihui Zhao¹, Luan Chen¹, Hailiang Huang³, Cong Huai¹, Xiaoqing Zhang⁴, Jinghong Zhang⁵, Wei Zhou¹, Lu Shen¹, Qi Zhen⁶, Bao Li⁶, Wenjun Wang⁶, Lin He⁷, Shengying Qin⁸

Affiliations

¹ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China.
² Department of Epidemiology, China and Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai 200032, China.
³ Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
⁴ Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.
⁵ Center for Tuberculosis Control and Prevention, Shandong Provincial Chest Hospital, Jinan, Shandong 250013, China.
⁶ Department of Dermatology, No. 1 Hospital and Key Laboratory of Dermatology (Ministry of Education), Anhui Medical University, Hefei, Anhui 230032, China.
⁷ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
⁸ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China; Collaborative Innovation Center, Jining Medical University, Jining, Shandong 272067, China. Electronic address: chinsir@sjtu.edu.cn.

PMID: 34052317
DOI: 10.1016/j.ygeno.2021.05.035

Abstract

The genetic factors of tuberculosis (TB) susceptibility have been widely recognized. Here we performed a two-stage study in 616 TB patients and 709 healthy controls to systematically identify the genetic markers of TB susceptibility. In the discovery stage, we identified 93 single nucleotide polymorphisms (SNPs) and 3 human leucocyte antigen (HLA) class II alleles that had potential associations with TB susceptibility. In the validation stage, we confirmed that 6 nominally significant SNPs, including 2 novel missense variants at RAB17 and DCTN4 (odds ratio (OR) = 1.40, P = 4.98 × 10^-3 and OR = 2.30, P = 3.17 × 10^-2 respectively), were associated with the predisposition to TB. Moreover, our study found that HLA-II allele DQA1*05:05 (P = 0.0011, OR = 1.44, 95%CI = 1.15-1.77) was a TB susceptibility locus for the first time. This study comprehensively investigated the genetic variants that were associated with TB susceptibility and provided insight into the tuberculosis pathogenesis.

Keywords: Genetic susceptibility; Genome-wide association study; Human leucocyte antigen; Tuberculosis; Whole-exome sequencing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alleles
Case-Control Studies
China
Genetic Predisposition to Disease
Genome-Wide Association Study*
Genotype
High-Throughput Nucleotide Sequencing
Humans
Polymorphism, Single Nucleotide
Tuberculosis* / genetics