ArticleAmerican journal of human genetics2021
Human ancient DNA analyses reveal the high burden of tuberculosis in Europeans over the last 2,000 years.
Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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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.
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Who cites it
63 citing papers in PubMed, 100 citations in OpenAlex.
- Ancient DNA and Human Physiology.Physiology (Bethesda, Md.) · 2026Review
- Humans homozygous for rare or common hypomorphic IL23R variants are prone to tuberculosis.The Journal of experimental medicine · 2026Article
- Article
- Toward a monogenic architecture of human infections: From 1996 to 2026.Journal of human immunity · 2026Review
- Insights into infectious diseases through ancient pathogen genomics.Nature reviews. Microbiology · 2026Review
- Article
- Ancient DNA reveals that natural selection has upregulated the immune system over the last 10,000 years.bioRxiv : the preprint server for biology · 2026Article
- How Genomic and Structural Context Could Shape JAK-STAT Variant Pathogenicity.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2026Article
- Monogenic disorders of immunity: Common variants are not so rare.Cell genomics · 2026Review
- Quarantine as filter: a conceptual framework from early modern Venice.Evolution, medicine, and public health · 2026Review
- Rethinking TYK2 P1104A: a flawed evolutionary trade-off in tuberculosis?Frontiers in immunology · 2026Review
- Ancient DNA insights into diverse pathogens and their hosts.Nature reviews. Genetics · 2026Review
- A human YEATS4 variant confers resistance to TST and IGRA conversion despite Mycobacterium tuberculosis exposure.Genome medicine · 2025Article
- Genetic Susceptibility to Tuberculosis and the Utility of Polygenic Scores in Population Stratification.International journal of molecular sciences · 2025Review
- SimOutbreakSelection: a simulation-based tool to optimise sampling design and analysis strategies for detecting epidemic-driven selection.Nature communications · 2025Article
- Human LY9 governs CD4Science immunology · 2025Article
- TYK2 :p.Pro1104Ala Variant Protects Against Autoimmunity by Modulating Immune Cell Levels.Immunology · 2025Article
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- Single nucleotide polymorphisms in IFN-gamma, TNF-alpha, IL-6, IL-10, and TGF-beta in pulmonary and extrapulmonary tuberculosis in the State of Ceará, northeastern Brazil.Memorias do Instituto Oswaldo Cruz · 2025Article
- The Microbe, the Infection Enigma, and the Host.Annual review of microbiology · 2024Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Tuberculosis (TB), usually caused by Mycobacterium tuberculosis bacteria, is the first cause of death from an infectious disease at the worldwide scale, yet the mode and tempo of TB pressure on humans remain unknown. The recent discovery that homozygotes for the P1104A polymorphism of TYK2 are at higher risk to develop clinical forms of TB provided the first evidence of a common, monogenic predisposition to TB, offering a unique opportunity to inform on human co-evolution with a deadly pathogen. Here, we investigate the history of human exposure to TB by determining the evolutionary trajectory of the TYK2 P1104A variant in Europe, where TB is considered to be the deadliest documented infectious disease. Leveraging a large dataset of 1,013 ancient human genomes and using an approximate Bayesian computation approach, we find that the P1104A variant originated in the common ancestors of West Eurasians ∼30,000 years ago. Furthermore, we show that, following large-scale population movements of Anatolian Neolithic farmers and Eurasian steppe herders into Europe, P1104A has markedly fluctuated in frequency over the last 10,000 years of European history, with a dramatic decrease in frequency after the Bronze Age. Our analyses indicate that such a frequency drop is attributable to strong negative selection starting ∼2,000 years ago, with a relative fitness reduction on homozygotes of 20%, among the highest in the human genome. Together, our results provide genetic evidence that TB has imposed a heavy burden on European health over the last two millennia.
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