A common NFKB1 variant detected through antibody analysis in UK Biobank predicts risk of infection and allergy.

Autor:	Chong AY; The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK. Electronic address: amanda.chong@well.ox.ac.uk., Brenner N; Division of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Jimenez-Kaufmann A; Advanced Genomics Unit, National Laboratory of Genomics for Biodiversity (LANGEBIO), CINVESTAV, Irapuato, Mexico., Cortes A; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK., Hill M; MRC-Population Health Research Unit, University of Oxford, Oxford, UK., Littlejohns TJ; Nuffield Department of Population Health, University of Oxford, Oxford, UK., Gilchrist JJ; The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; Department of Paediatrics, University of Oxford, Oxford, UK., Fairfax BP; Department of Oncology, University of Oxford, Oxford, UK., Knight JC; The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Hodel F; Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland., Fellay J; Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland; Precision Medicine Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., McVean G; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK., Moreno-Estrada A; Advanced Genomics Unit, National Laboratory of Genomics for Biodiversity (LANGEBIO), CINVESTAV, Irapuato, Mexico., Waterboer T; Division of Infections and Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Hill AVS; The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; The Jenner Institute, University of Oxford, Oxford, UK., Mentzer AJ; The Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK. Electronic address: alexander.mentzer@ndm.ox.ac.uk.
Jazyk:	angličtina
Zdroj:	American journal of human genetics [Am J Hum Genet] 2024 Feb 01; Vol. 111 (2), pp. 295-308. Date of Electronic Publication: 2024 Jan 16.
DOI:	10.1016/j.ajhg.2023.12.013
Abstrakt:	Infectious agents contribute significantly to the global burden of diseases through both acute infection and their chronic sequelae. We leveraged the UK Biobank to identify genetic loci that influence humoral immune response to multiple infections. From 45 genome-wide association studies in 9,611 participants from UK Biobank, we identified NFKB1 as a locus associated with quantitative antibody responses to multiple pathogens, including those from the herpes, retro-, and polyoma-virus families. An insertion-deletion variant thought to affect NFKB1 expression (rs28362491), was mapped as the likely causal variant and could play a key role in regulation of the immune response. Using 121 infection- and inflammation-related traits in 487,297 UK Biobank participants, we show that the deletion allele was associated with an increased risk of infection from diverse pathogens but had a protective effect against allergic disease. We propose that altered expression of NFKB1, as a result of the deletion, modulates hematopoietic pathways and likely impacts cell survival, antibody production, and inflammation. Taken together, we show that disruptions to the tightly regulated immune processes may tip the balance between exacerbated immune responses and allergy, or increased risk of infection and impaired resolution of inflammation. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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