A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

BackgroundThere is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia.MethodsIn stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia.ResultsOur study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4.ConclusionsMechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.

• Publication year

  2012

• Venue

  BMC Medical Genetics

• Publication date

  2012-01-13

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1186/1471-2350-13-5PMID 22239941PMCID 3287960
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• SLC11A1 (NRAMP1) Polymorphisms and Tuberculosis Susceptibility: Updated Systematic Review and Meta-Analysis

  2011cited by this paper
• Genome-wide association analyses identifies a susceptibility locus for tuberculosis on chromosome 18q11.2

  2010influential reference
• ADAM17 regulates epidermal growth factor receptor expression through the activation of Notch1 in non-small cell lung cancer.

  2010cited by this paper
• Ectodomain shedding of the Notch ligand Jagged1 is mediated by ADAM17, but is not a lipid-raft-associated event.

  2010influential reference
• Polimorfismos do gene NRAMP1 em indivíduos com reações hansênicas, atendidos em dois Centros de Referência no Recife, nordeste do Brasil

  2010cited by this paper
• Genomewide association study of leprosy.

  2010cited by this paper
• [NRAMP1 gene polymorphisms in individuals with leprosy reactions attended at two reference centers in Recife, northeastern Brazil].

  2010cited by this paper
• A Disintegrin and Metalloproteinase 17 (ADAM17) Mediates Inflammation-induced Shedding of Syndecan-1 and -4 by Lung Epithelial Cells*

  2009cited by this paper
• Genomewide association study of leprosy.

  2009cited by this paper
• Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis

  2008cited by this paper
• Launching the T-cell-lineage developmental programme

  2008cited by this paper
• NOTCH1 Up-regulation and Signaling Involved in Mycobacterium bovis BCG-induced SOCS3 Expression in Macrophages*

  2008cited by this paper
• Phorbol Ester-induced Shedding of the Prostate Cancer Marker Transmembrane Protein with Epidermal Growth Factor and Two Follistatin Motifs 2 Is Mediated by the Disintegrin and Metalloproteinase-17*

  2007cited by this paper
• Association of polymorphisms in IL-12/IFN-gamma pathway genes with susceptibility to pulmonary tuberculosis in Indonesia.

  2007cited by this paper
• PLINK: a tool set for whole-genome association and population-based linkage analyses.

  2007cited by this paper
• Resequencing and association analysis of the SP110 gene in adult pulmonary tuberculosis

  2007influential reference
• The transcriptional regulation of B cell lineage commitment.

  2007cited by this paper
• Pax5: the guardian of B cell identity and function

  2007cited by this paper
• Principal components analysis corrects for stratification in genome-wide association studies

  2006cited by this paper
• Dynamic Changes in Pro- and Anti-Inflammatory Cytokine Profiles and Gamma Interferon Receptor Signaling Integrity Correlate with Tuberculosis Disease Activity and Response to Curative Treatment

  2006cited by this paper
• Evaluating coverage of genome-wide association studies

  2006cited by this paper
• Coverage and Characteristics of the Affymetrix GeneChip Human Mapping 100K SNP Set

  2006cited by this paper
• An autosomal dominant major gene confers predisposition to pulmonary tuberculosis in adults

  2006cited by this paper
• Diabetes mellitus is strongly associated with tuberculosis in Indonesia.

  2006cited by this paper
• A genotype calling algorithm for affymetrix SNP arrays

  2006cited by this paper
• A genome-wide scalable SNP genotyping assay using microarray technology

  2005cited by this paper
• Ipr1 gene mediates innate immunity to tuberculosis

  2005cited by this paper
• Confounding from Cryptic Relatedness in Case-Control Association Studies

  2005cited by this paper
• A high-density admixture map for disease gene discovery in african americans.

  2004cited by this paper
• Fringe glycosyltransferases differentially modulate Notch1 proteolysis induced by Delta1 and Jagged1.

  2004cited by this paper
• Genotyping over 100,000 SNPs on a pair of oligonucleotide arrays

  2004cited by this paper
• Cytokine-chemokine networks in experimental mycobacterial and schistosomal pulmonary granuloma formation.

  2003cited by this paper
• Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits

  2003cited by this paper
• The growing burden of tuberculosis: global trends and interactions with the HIV epidemic.

  2003cited by this paper
• Genetic dissection of immunity to mycobacteria: the human model.

  2002cited by this paper
• Genetic Structure of Human Populations

  2002cited by this paper
• Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae

  2002cited by this paper
• Global tuberculosis control report.

  2001cited by this paper
• Genetic Regulation of Acquired Immune Responses to Antigens of Mycobacterium tuberculosis: a Study of Twins in West Africa

  2001cited by this paper
• Genetic Regulation of Acquired Immune Responses to Antigens ofMycobacterium tuberculosis: a Study of Twins in West Africa

  2001cited by this paper
• Improved inference of relationship for pairs of individuals.

  2000cited by this paper
• Lifetime risks, incubation period, and serial interval of tuberculosis.

  2000cited by this paper
• Genetic susceptibility to tuberculosis in Africans: a genome-wide scan.

  2000cited by this paper
• Genomic Control for Association Studies

  1999influential reference
• Twin Studies on the Significance of Genetic Factors in Tuberculosis1,2

  1943cited by this paper
• Bmc Medical Genetics

  year unknowncited by this paper

• ASAP1 as a novel dual-level biomarker for tuberculosis: integrated genetic and proteomic evidence for early detection and disease monitoring

  2026cites this paper
• Genetic Susceptibility to Tuberculosis and the Utility of Polygenic Scores in Population Stratification

  2025cites this paper
• The need for interconnected global biorepositories from tuberculosis studies to address fundamental questions at scale.

  2025cites this paper
• Myeloid cell genome-wide screen identifies variants associated with Mycobacterium tuberculosis–induced cytokine transcriptional responses

  2025cites this paper
• A human YEATS4 variant confers resistance to TST and IGRA conversion despite Mycobacterium tuberculosis exposure

  2025cites this paper
• Genome-wide association study in Brazil identifies risk factor-adjusted genetic susceptibility to pulmonary tuberculosis with cell-specific gene expression effects

  2025cites this paper
• BCG induced innate immune response heterogeneity and susceptibility to pediatric tuberculosis.

  2025cites this paper
• Uncharted territory: the role of mitochondrial DNA variation in macrophage-mediated host susceptibility to tuberculosis.

  2025cites this paper
• X-linked multi-ancestry meta-analysis reveals tuberculosis susceptibility variants

  2024cites this paper
• Genetic association of missense (rs2919643), intergenic (rs2057178) and a 3'UTR (rs1009170) variant with tuberculosis: A replication study from India.

  2024cites this paper
• Genome-wide host-pathogen analyses reveal genetic interaction points in tuberculosis disease

  2023cites this paper
• REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk

  2022cites this paper
• Genetic architecture of tuberculosis susceptibility: A comprehensive research synopsis, meta-analyses, and epidemiological evidence.

  2022cites this paper
• The immunogenetics of tuberculosis (TB) susceptibility

  2022cites this paper
• Study of HLA-G gene polymorphism and serum level of soluble HLA-G in patients infected with Mycobacterium tuberculosis

  2022cites this paper
• Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture

  2022cites this paper
• CNBP, REL, and BHLHE40 variants are associated with IL-12 and IL-10 responses and tuberculosis risk

  2021cites this paper
• A multi-phenotype genome-wide association study of clades causing tuberculosis in a Ghanaian- and South African cohort.

  2021cites this paper
• Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients

  2021cites this paper
• An AutoML Approach for Predicting Risk of Progression to Active Tuberculosis based on Its Association with Host Genetic Variations

  2021cites this paper
• Local Ancestry Adjusted Allelic Association Analysis Robustly Captures Tuberculosis Susceptibility Loci

  2021cites this paper
• Macrophage migration inhibitory factor − 794 CATT5−8 microsatellite polymorphism and susceptibility of tuberculosis

  2021cites this paper
• Allelic and Genotypic Frequencies of NAT2, CYP2E1 and AADAC genes in a cohort of Peruvian Tuberculosis Patients

  2021cites this paper
• A regulatory variant in the C1Q gene cluster is associated with tuberculosis susceptibility and C1qA plasma levels in a South African population

  2020cites this paper
• Integrative genomics analysis identifies promising SNPs and genes implicated in tuberculosis risk based on multiple omics datasets

  2020cites this paper
• A multi-phenotype genome-wide association study of clades causing tuberculosis in a Ghanaian- and South African cohort

  2020cites this paper
• Natural Resistance to and Host-Directed Prevention of Tuberculosis

  2020cites this paper
• Tuberculosis risk is associated with genetic polymorphisms in the LRP2, CUBN, and VDR genes

  2020cites this paper
• Macrophage migration inhibitory factor -173 G>C single nucleotide polymorphism and its association with active pulmonary tuberculosis

  2020cites this paper
• Can the personalized medicine approach contribute in controlling tuberculosis in general and India in particular?

  2020cites this paper
• These Are the Genes You're Looking For: Finding Host Resistance Genes.

  2020cites this paper
• Genetics of Infectious Diseases

  2019cites this paper
• An exome wide association study of pulmonary tuberculosis patients and their asymptomatic household contacts.

  2019cites this paper
• Homozygosity for TYK2 P1104A underlies tuberculosis in about 1% of patients in a cohort of European ancestry

  2019cites this paper
• ASAP1 gene polymorphisms are associated with susceptibility to tuberculosis in a Chinese Xinjiang Muslim population

  2018cites this paper
• Validation of the Results of Genome-Wide Association Studies of Tuberculosis in Russians of West Siberia

  2018cites this paper
• The Role of Single Nucleotide Polymorphisms in C-Type Lectin Receptors and the Signaling Molecules in their Pathways in Susceptibility towards developing Pulmonary Tuberculosis in an Indian Population

  2018cites this paper
• A Sex-Stratified Genome-Wide Association Study of Tuberculosis Using a Multi-Ethnic Genotyping Array

  2018cites this paper
• Detrimental association between diabetes and tuberculosis: An unresolved double trouble.

  2018cites this paper
• A bioinformatic analysis of Mycobacterium tuberculosis and host genomic data

  2018cites this paper
• Fine-mapping Analysis of a Chromosome 2 Region Linked to Resistance to Mycobacterium tuberculosis Infection in Uganda Reveals Potential Regulatory Variants

  2018cites this paper
• Human genetics of mycobacterial disease

  2018cites this paper
• Survival of Lung Cancer Patients in Dr Wahidin Sudirohusodo Hospital Makassar 2012-2016

  2018cites this paper
• IL1R1 and IL1R2 polymorphisms were associated with tuberculosis risk: A pilot study

  2018cites this paper
• Genetic Resistance to Mycobacterium tuberculosis Infection and Disease

  2018cites this paper
• Genome-wide association study identifies two risk loci for tuberculosis in Han Chinese

  2018cites this paper
• The arms race between man and Mycobacterium tuberculosis: Time to regroup.

  2017cites this paper
• Genomics of Human Pulmonary Tuberculosis: from Genes to Pathways

  2017cites this paper
• A post-GWAS analysis of predicted regulatory variants and tuberculosis susceptibility

  2017cites this paper
• Risk prediction of pulmonary tuberculosis using genetic and conventional risk factors in adult Korean population

  2017cites this paper
• Mannose-Binding Lectin (MBL) gene polymorphisms in susceptibility to pulmonary tuberculosis among the Lur population of Lorestan Province of Iran

  2017cites this paper
• Association of IFNGR1 and IFNG genetic polymorphisms with the risk for pulmonary tuberculosis in the Chinese Tibetan population

  2017cites this paper
• Discovery of susceptibility loci associated with tuberculosis in Han Chinese

  2017influential citation
• Predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells

  2017cites this paper
• Association between SLC11A1 (NRAMP1) polymorphisms and susceptibility to tuberculosis in Chinese Holstein cattle.

  2017cites this paper
• Pathogen lineage-based genome-wide association study identified CD53 as susceptible locus in tuberculosis

  2017cites this paper
• Differential genetic background of primary and secondary tuberculosis in Russians

  2017cites this paper
• The role of human host genetics in tuberculosis resistance

  2017cites this paper
• Human Genomics of Mycobacterium tuberculosis Infection and Disease

  2017cites this paper
• Genes and Genetics of Tuberculosis

  2017influential citation
• Tuberculosis and diabetes: current state and future perspectives

  2016cites this paper
• Identification of ITPA on chromosome 20 as a susceptibility gene for young-onset tuberculosis

  2016cites this paper
• Do HLA class II genes protect against pulmonary tuberculosis? A systematic review and meta-analysis

  2016cites this paper
• The Role of Host Genetics (and Genomics) in Tuberculosis

  2016cites this paper
• A genome-wide association study of pulmonary tuberculosis in Morocco

  2016cites this paper
• Network Analysis of Human Genes Influencing Susceptibility to Mycobacterial Infections

  2016cites this paper
• Association of genetic polymorphisms with pulmonary tuberculosis in a Chinese Tibetan population : a case-control study

  2016cites this paper
• Beta-defensin gene (DEFB1) polymorphisms are associated with the susceptibility to chronic respiratory diseases

  2016influential citation
• Association of rs4331426 and rs2057178 with Risk of Tuberculosis: Evidence from a Meta-Analysis

  2016cites this paper
• The genetics of susceptibility to tuberculosis: Progress and challenges

  2016cites this paper
• Association between TNF -308G/A polymorphism and susceptibility to pulmonary tuberculosis in the Lur population of Iran

  2016cites this paper
• Interleukin-10 -1082A>G polymorphism and susceptibility to pulmonary Tuberculosis in Lur population of Iran.

  2016cites this paper
• Deciphering Genetic Susceptibility to Tuberculous Meningitis

  2016cites this paper
• Genetic and Genomic Landscape of Tuberculosis

  2016cites this paper
• Mutations in genes underlying atypical familial mycobacteriosis are not found in tuberculosis patients from Siberian populations.

  2015cites this paper
• Investigation of Toll-Like Receptor-2 (2258G/A) and Interferon Gamma (+874T/A) Gene Polymorphisms among Infertile Women with Female Genital Tuberculosis

  2015cites this paper
• Interleukin-10 Promoter Gene Polymorphisms and Susceptibility to Tuberculosis: A Meta-Analysis

  2015cites this paper
• Common polymorphisms in the CD43 gene region are associated with tuberculosis disease and mortality.

  2015cites this paper
• Association of Polymorphisms in Toll-Like Receptors 4 and 9 with Risk of Pulmonary Tuberculosis: A Meta-Analysis

  2015cites this paper
• Predicting functional regulatory SNPs in the human antimicrobial peptide genes DEFB1 and CAMP in tuberculosis and HIV/AIDS

  2015cites this paper
• Acquired immunodeficiencies and tuberculosis: focus on HIV/AIDS and diabetes mellitus

  2015cites this paper
• TLR1, 2, 4, 6 and 9 Variants Associated with Tuberculosis Susceptibility: A Systematic Review and Meta-Analysis

  2015cites this paper
• TLR 1 , 2 , 4 , 6 and 9 Variants Associated with Tuberculosis Susceptibility : A Systematic Review and Meta-Analysis

  2015cites this paper
• Single Nucleotide Polymorphisms in P2X7 Gene Are Associated with Serum Immunoglobulin G Responses to Mycobacterium tuberculosis in Tuberculosis Patients

  2015cites this paper
• FOXO3 rs12212067: T > G Association with Active Tuberculosis in Han Chinese Population

  2015cites this paper
• The role of the major histocompatibility complex and the Leukocyte receptor complex genes in susceptibility to tuberculosis in a South African population

  2014cites this paper
• Risk factors for treatment failure in isoniazid resistant tuberculosis

  2014cites this paper
• Host genome polymorphisms and tuberculosis infection: What we have to say?

  2014cites this paper
• Host genetic studies in adult pulmonary tuberculosis.

  2014cites this paper
• Natural selection and infectious disease in human populations

  2014cites this paper
• Bayesian neural networks for detecting epistasis in genetic association studies

  2014cites this paper
• Understanding the Genetic Etiology of Complex Phenotypes using Bayesian Neural Networks

  2014cites this paper
• TuberculosisImmune Gene Polymorphisms in

  2014cites this paper
• Functional polymorphism in aldehyde dehydrogenase-2 gene associated with risk of tuberculosis

  2014cites this paper
• Association between the PTPN22 1858C/T gene polymorphism and tuberculosis resistance.

  2013cites this paper
• Nucleotide variation in IL‐10 and IL‐12 and their receptors and cervical and vulvar cancer risk: A hybrid case–parent triad and case–control study

  2013cites this paper
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  2013cites this paper
• SEARCH OF TUBERCULOSIS SUSCEPTIBILITY GENES USING THE RESULTS OF GENOME-WIDE ASSOCIATION STUDY OF CROHN’S DISEASE

  2013cites this paper
• [Advances in genome-wide association study of tuberculosis].

  2013influential citation
• IL‐12Rβ1 Deficiency: Mutation Update and Description of the IL12RB1 Variation Database

  2013cites this paper