Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern EuropeansResearch in context
Summary: Background: The hypomorphic variant rs11209026-A in the IL23R gene provides significant protection against immune-related diseases in Europeans, notably inflammatory bowel diseases (IBD). Today, the A-allele occurs with an average frequency of 5% in Europe. Methods: This study comprised 25...
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Elsevier
2025-03-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425000350 |
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| author | Ben Krause-Kyora Nicolas Antonio da Silva Elif Kaplan Daniel Kolbe Inken Wohlers Hauke Busch David Ellinghaus Amke Caliebe Efe Sezgin Almut Nebel Stefan Schreiber Sabine Schade-Lindig Joachim Wahl Carola Berszin Michael Francken Irina Görner Kerstin Schierhold Joachim Pechtl Gisela Grupe Johannes Müller |
| author_facet | Ben Krause-Kyora Nicolas Antonio da Silva Elif Kaplan Daniel Kolbe Inken Wohlers Hauke Busch David Ellinghaus Amke Caliebe Efe Sezgin Almut Nebel Stefan Schreiber Sabine Schade-Lindig Joachim Wahl Carola Berszin Michael Francken Irina Görner Kerstin Schierhold Joachim Pechtl Gisela Grupe Johannes Müller |
| author_sort | Ben Krause-Kyora |
| collection | DOAJ |
| description | Summary: Background: The hypomorphic variant rs11209026-A in the IL23R gene provides significant protection against immune-related diseases in Europeans, notably inflammatory bowel diseases (IBD). Today, the A-allele occurs with an average frequency of 5% in Europe. Methods: This study comprised 251 ancient genomes from Europe spanning over 14,000 years. In these samples, the investigation focused on admixture-informed analyses and selection scans of rs11209026-A and its haplotypes. Findings: rs11209026-A was found at high frequencies in Anatolian Farmers (AF, 18%). AF later introduced the allele into the ancient European gene-pool. Subsequent admixture caused its frequency to decrease and formed the current southwest-to-northeast allele frequency cline in Europe. The geographic distribution of rs11209026-A may influence the gradient in IBD incidence rates that are highest in northern and eastern Europe. Interpretation: Given the dramatic changes from hunting and gathering to agriculture during the Neolithic, AF might have been exposed to selective pressures from a pro-inflammatory lifestyle and diet. Therefore, the protective A-allele may have increased survival by reducing intestinal inflammation and microbiome dysbiosis. The adaptively evolved function of the variant likely contributes to the high efficacy and low side-effects of modern IL-23 neutralisation therapies for chronic inflammatory diseases. Funding: German Research Foundation (EXC 2167 390884018 and EXC 2150 390870439). |
| format | Article |
| id | doaj-art-64c8ea62fad74534b601b000277019dd |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-64c8ea62fad74534b601b000277019dd2025-02-10T04:34:35ZengElsevierEBioMedicine2352-39642025-03-01113105591Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern EuropeansResearch in contextBen Krause-Kyora0Nicolas Antonio da Silva1Elif Kaplan2Daniel Kolbe3Inken Wohlers4Hauke Busch5David Ellinghaus6Amke Caliebe7Efe Sezgin8Almut Nebel9Stefan Schreiber10Sabine Schade-LindigJoachim WahlCarola BerszinMichael FranckenIrina GörnerKerstin SchierholdJoachim PechtlGisela GrupeJohannes MüllerInstitute of Clinical Molecular Biology, Kiel University, Kiel, Germany; Corresponding author. Institute for Clinical Molecular Biology, Kiel University, Rosalind-Franklin-Strasse 12, Kiel, 24105, Germany.Institute of Clinical Molecular Biology, Kiel University, Kiel, GermanyInstitute of Clinical Molecular Biology, Kiel University, Kiel, GermanyInstitute of Clinical Molecular Biology, Kiel University, Kiel, GermanyBiomolecular Data Science in Pneumology, Research Center Borstel, Borstel, Germany; University of Lübeck, Lübeck, GermanyLübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, GermanyInstitute of Clinical Molecular Biology, Kiel University, Kiel, GermanyInstitute of Medical Informatics and Statistics, Kiel University, Kiel, GermanyDepartment of Food Engineering, Izmir Institute of Technology, Urla, Izmir, TurkeyInstitute of Clinical Molecular Biology, Kiel University, Kiel, GermanyInstitute of Clinical Molecular Biology, Kiel University, Kiel, Germany; Department for Medicine I, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Corresponding author. Department of Medicine I, Kiel University, University Hospital Schleswig-Holstein, Rosalind-Franklin-Strasse 12, Kiel, 24105, Germany.Summary: Background: The hypomorphic variant rs11209026-A in the IL23R gene provides significant protection against immune-related diseases in Europeans, notably inflammatory bowel diseases (IBD). Today, the A-allele occurs with an average frequency of 5% in Europe. Methods: This study comprised 251 ancient genomes from Europe spanning over 14,000 years. In these samples, the investigation focused on admixture-informed analyses and selection scans of rs11209026-A and its haplotypes. Findings: rs11209026-A was found at high frequencies in Anatolian Farmers (AF, 18%). AF later introduced the allele into the ancient European gene-pool. Subsequent admixture caused its frequency to decrease and formed the current southwest-to-northeast allele frequency cline in Europe. The geographic distribution of rs11209026-A may influence the gradient in IBD incidence rates that are highest in northern and eastern Europe. Interpretation: Given the dramatic changes from hunting and gathering to agriculture during the Neolithic, AF might have been exposed to selective pressures from a pro-inflammatory lifestyle and diet. Therefore, the protective A-allele may have increased survival by reducing intestinal inflammation and microbiome dysbiosis. The adaptively evolved function of the variant likely contributes to the high efficacy and low side-effects of modern IL-23 neutralisation therapies for chronic inflammatory diseases. Funding: German Research Foundation (EXC 2167 390884018 and EXC 2150 390870439).http://www.sciencedirect.com/science/article/pii/S2352396425000350IL23RIL-23-signallingAncient genomicsCrohn's diseaseUlcerative colitisInflammatory bowel diseases |
| spellingShingle | Ben Krause-Kyora Nicolas Antonio da Silva Elif Kaplan Daniel Kolbe Inken Wohlers Hauke Busch David Ellinghaus Amke Caliebe Efe Sezgin Almut Nebel Stefan Schreiber Sabine Schade-Lindig Joachim Wahl Carola Berszin Michael Francken Irina Görner Kerstin Schierhold Joachim Pechtl Gisela Grupe Johannes Müller Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern EuropeansResearch in context EBioMedicine IL23R IL-23-signalling Ancient genomics Crohn's disease Ulcerative colitis Inflammatory bowel diseases |
| title | Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern EuropeansResearch in context |
| title_full | Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern EuropeansResearch in context |
| title_fullStr | Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern EuropeansResearch in context |
| title_full_unstemmed | Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern EuropeansResearch in context |
| title_short | Neolithic introgression of IL23R-related protection against chronic inflammatory bowel diseases in modern EuropeansResearch in context |
| title_sort | neolithic introgression of il23r related protection against chronic inflammatory bowel diseases in modern europeansresearch in context |
| topic | IL23R IL-23-signalling Ancient genomics Crohn's disease Ulcerative colitis Inflammatory bowel diseases |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425000350 |
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