ArticleNature genetics2018
Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis.
Erratum issuedOpen access · hybridAbstract read
In one paragraph
Article in Nature genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 212 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
212citing papers in PubMed, 2 pooled it
27.5field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
212 citing papers in PubMed, 2 syntheses or guidelines pooled it, 423 citations in OpenAlex.
- In Host Mutational Adaptation of Mycobacterium Tuberculosis Complex Strains During Tuberculosis Infection.The Journal of infectious diseases · 2026Pooled it
- Open-access genomic drug resistance prediction tools forJournal of clinical microbiology · 2026Pooled it
- The structural context of mutations in proteins predicts their effect on antibiotic resistance.eLife · 2026Article
- Current Landscape of Molecular Diagnostic Tests and Emerging Tools for Tuberculosis and Drug Resistance.Diagnostics (Basel, Switzerland) · 2026Review
- Identification and Evaluation of Dibasic Piperidines as Cell Wall Inhibitors againstACS infectious diseases · 2026Article
- A versatile multi-components mixed model for bacterial-Genome Wide association studies.Nature communications · 2026Article
- Genetic Characterization of First-Line Drug-Resistance Mutations in Multidrug-ResistantPathogens (Basel, Switzerland) · 2026Article
- Capsular specificity in temperate phages of Klebsiella pneumoniae is driven by diverse receptor-binding enzymes.PLoS biology · 2026Article
- Mutations in sugar metabolism-related genes driving global drug-resistant Mycobacterium tuberculosis transmission revealed by whole-genome sequencing.BMC infectious diseases · 2026Article
- Identification and Evaluation of dibasic piperidines as novel cell wall inhibitors againstbioRxiv : the preprint server for biology · 2026Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Respiratory chain gene mutations associated with global phylogenetic clustering of drug-resistantFrontiers in immunology · 2026Article
- Functional genomics reveals strain-specific genetic requirements conferring hypoxic growth ineLife · 2025Article
- Zinc pyrithione impairs iron-sulfur cluster biogenesis in Mycobacterium tuberculosis.BMC microbiology · 2025Article
- An explainable artificial intelligence framework reveals mutations associated with drug resistance inBiosafety and health · 2025Article
- TOAST: a novel tool for designing targeted gene amplicons and an optimised set of primers for high-throughput sequencing in tuberculosis genomic studies.BMC genomics · 2025Article
- Unraveling Epistatic Interactions Between Sites Under Drug-Dependent Selection in the Mycobacterium tuberculosis Genome.Molecular biology and evolution · 2025Article
- Article
- Genomic decoding of drug-resistant tuberculosis transmission in Thailand over three decades.Scientific reports · 2025Article
- UShER-TB: Scalable, Comprehensive, Accessible Phylogenomic Analysis ofmedRxiv : the preprint server for health sciences · 2025Article
152 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
51 authors at 20 institutions in 18 countries.
Francesc CollFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.ORCID http://orcid.org/0000-0002-7882-2325
Jody PhelanFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Grant A Hill-CawthornePathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.ORCID http://orcid.org/0000-0002-3828-5473
Mridul B NairPathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Kim MallardFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Shahjahan AliPathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Abdallah M AbdallahPathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Saad AlghamdiLaboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia.
Mona AlsomaliPathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Abdallah O AhmedDepartment of Microbiology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Stephanie PortelliFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Yaa OppongFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Adriana AlvesNational Mycobacterium Reference Laboratory, Porto, Portugal.
Theolis Barbosa BessaCentro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.
Susana CampinoFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Maxine CawsLiverpool School of Tropical Medicine, Liverpool, UK.
Anirvan ChatterjeeFoundation for Medical Research, Mumbai, India.
Amelia C CrampinFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
Keertan DhedaLung Infection and Immunity Unit, UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa.
Nicholas FurnhamFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Judith R GlynnFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.ORCID http://orcid.org/0000-0001-9325-4576
Louis GrandjeanLaboratorio de Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
Dang Minh HaPham Ngoc Thach Hospital for TB and Lung Diseases, Ho Chi Minh City, Vietnam.
Rumina HasanDepartment of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan.
Zahra HasanDepartment of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan.
Martin L HibberdFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Moses JolobaDepartment of Medical Microbiology, Makerere University College of Health Sciences, Kampala, Uganda.
Edward C Jones-LópezSection of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, MA, USA.
Tomoshige MatsumotoOsaka Anti-Tuberculosis Association, Osaka Hospital, Osaka, Japan.
Anabela MirandaNational Mycobacterium Reference Laboratory, Porto, Portugal.
David J MooreFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.ORCID http://orcid.org/0000-0002-3748-0154
Nora MocilloReference Laboratory of Tuberculosis Control, Buenos Aires, Argentina.
Stefan PanaiotovNational Center of Infectious and Parasitic Diseases, Sofia, Bulgaria.
Julian ParkhillWellcome Trust Sanger Institute, Hinxton, UK.ORCID http://orcid.org/0000-0002-7069-5958
Carlos PenhaInstituto Gulbenkian de Ciência, Lisbon, Portugal.
João PerdigãoiMed.ULisboa-Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal.
Isabel PortugaliMed.ULisboa-Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal.
Zineb RchiadPathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia.
Jaime RobledoCorporación para Investigaciones Biológicas, Universidad Pontificia Bolivariana, Medellín, Colombia.ORCID http://orcid.org/0000-0002-5731-1905
Patricia SheenLung Infection and Immunity Unit, UCT Lung Institute, University of Cape Town, Groote Schuur Hospital, Cape Town, South Africa.
Nashwa Talaat SheshaRegional Laboratory Directorate of Health Affairs, Makkah, Saudi Arabia.
Frik A SirgelDivision of Molecular Biology and Human Genetics, SAMRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Christophe SolaInstitute for Integrative Cell Biology, CEA, CNRS, Université Paris-Saclay, Orsay, France.
Erivelton Oliveira SousaCentro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil.
Elizabeth M StreicherDivision of Molecular Biology and Human Genetics, SAMRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Paul Van HeldenDivision of Molecular Biology and Human Genetics, SAMRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Miguel ViveirosUnidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (UNL), Lisbon, Portugal.ORCID http://orcid.org/0000-0001-9676-6251
Robert M WarrenDivision of Molecular Biology and Human Genetics, SAMRC Centre for Tuberculosis Research, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Ruth McNerneyFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. ruth.mcnerney@uct.ac.za.ORCID http://orcid.org/0000-0003-0505-2291
Arnab PainPathogen Genomics Laboratory, BESE Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia. arnab.pain@kaust.edu.sa.ORCID http://orcid.org/0000-0002-1755-2819
Taane G ClarkFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK. taane.clark@lshtm.ac.uk.ORCID http://orcid.org/0000-0001-8985-9265
London School of Hygiene & Tropical Medicine · GBKing Abdullah University of Science and Technology · SASouth African Medical Research Council · ZAAga Khan University · PKFundação Oswaldo Cruz · BRUmm al-Qura University · SAUniversidad Peruana Cayetano Heredia · PEUniversity of Cape Town · ZAUniversity of Lisbon · PTBoston University · USCentre National de la Recherche Scientifique · FRFoundation for Medical Research · INHokkaido University · JPInstituto Gulbenkian de Ciência · PTLiverpool School of Tropical Medicine · GBMakerere University · UGNational Center of Infectious and Parasitic Diseases · BGOsaka Hospital · JPPham Ngoc Thach Hospital · VNThe University of Melbourne · AU
Funding
Medical Research Council MC_PC_15103Medical Research Council MR/K000551/1Medical Research Council MR/K020420/1Medical Research Council MR/M01360X/1Medical Research Council MR/N010469/1Wellcome Trust 098610Wellcome Trust 201344/Z/16/Z
Abstract
To characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps (drrA and Rv2688c) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms.
Indexed as
Genome, BacterialAntitubercular AgentsDNA, BacterialDrug Resistance, Multiple, BacterialExtensively Drug-Resistant TuberculosisGenetic VariationGenome-Wide Association StudyGeographyHumansMicrobial Sensitivity TestsMutationMycobacterium tuberculosisPhylogenySequence Analysis, DNATuberculosis, Multidrug-ResistantAntitubercular AgentsDNA, Bacterial
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