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      Identification of host–pathogen-disease relationships using a scalable multiplex serology platform in UK Biobank

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          Abstract

          Certain infectious agents are recognised causes of cancer and other chronic diseases. To understand the pathological mechanisms underlying such relationships, here we design a Multiplex Serology platform to measure quantitative antibody responses against 45 antigens from 20 infectious agents including human herpes, hepatitis, polyoma, papilloma, and retroviruses, as well as Chlamydia trachomatis, Helicobacter pylori and Toxoplasma gondii, then assayed a random subset of 9695 UK Biobank participants. We find seroprevalence estimates consistent with those expected from prior literature and confirm multiple associations of antibody responses with sociodemographic characteristics (e.g., lifetime sexual partners with C. trachomatis), HLA genetic variants (rs6927022 with Epstein-Barr virus (EBV) EBNA1 antibodies) and disease outcomes (human papillomavirus-16 seropositivity with cervical intraepithelial neoplasia, and EBV responses with multiple sclerosis). Our accessible dataset is one of the largest incorporating diverse infectious agents in a prospective UK cohort offering opportunities to improve our understanding of host-pathogen-disease relationships with significant clinical and public health implications.

          Abstract

          Here, the authors design a multiplex serology platform to quantitatively measure antibodies against 20 infectious agents in UK Biobank participants and confirm associations of antibody responses with sociodemographic characteristics, HLA genetic variants, and disease outcomes.

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          UK Biobank: An Open Access Resource for Identifying the Causes of a Wide Range of Complex Diseases of Middle and Old Age

          Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
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            The UK Biobank resource with deep phenotyping and genomic data

            The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.
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              Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis.

              The epidemiology of Helicobacter pylori infection has changed with improvements in sanitation and methods of eradication. We performed a systematic review and meta-analysis to evaluate changes in the global prevalence of H pylori infection.
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                Author and article information

                Contributors
                alexander.mentzer@ndm.ox.ac.uk
                T.Waterboer@dkfz-heidelberg.de
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                5 April 2022
                5 April 2022
                2022
                : 13
                : 1818
                Affiliations
                [1 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, The Wellcome Centre for Human Genetics, , University of Oxford, ; Oxford, UK
                [2 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, , University of Oxford, ; Oxford, UK
                [3 ]GRID grid.7497.d, ISNI 0000 0004 0492 0584, Division of Infections and Cancer Epidemiology, , German Cancer Research Center (DKFZ), ; Heidelberg, Germany
                [4 ]GRID grid.421945.f, ISNI 0000 0004 0396 0496, UK Biobank, ; Stockport, UK
                [5 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of Population Health, , University of Oxford, ; Oxford, UK
                [6 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, MRC-Population Health Research Unit, , University of Oxford, ; Oxford, UK
                [7 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, The Jenner Institute, , University of Oxford, ; Oxford, UK
                [8 ]GRID grid.10698.36, ISNI 0000000122483208, University of North Carolina at Chapel Hill, ; Chapel Hill, NC USA
                [9 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Department of Medicine, , Imperial College London, ; London, UK
                [10 ]GRID grid.271308.f, ISNI 0000 0004 5909 016X, Public Health England, ; Manchester, UK
                [11 ]GRID grid.83440.3b, ISNI 0000000121901201, Division of Infection and Immunity, , University College London, ; London, UK
                [12 ]GRID grid.271308.f, ISNI 0000 0004 5909 016X, Special Pathogens Reference Unit, , Public Health England, ; England, UK
                [13 ]GRID grid.418321.d, ISNI 0000 0004 1757 9741, Centro di Riferimento Oncologico, ; Aviano, Italy
                [14 ]GRID grid.5335.0, ISNI 0000000121885934, University of Cambridge, ; Cambridge, UK
                [15 ]GRID grid.8991.9, ISNI 0000 0004 0425 469X, London School of Hygiene and Tropical Medicine, ; London, UK
                [16 ]GRID grid.426108.9, ISNI 0000 0004 0417 012X, Royal Free Hospital, ; London, UK
                [17 ]GRID grid.439475.8, ISNI 0000 0004 6360 002X, Public Health Wales, ; Wales, UK
                [18 ]GRID grid.8348.7, ISNI 0000 0001 2306 7492, John Radcliffe Hospital, ; Oxford, UK
                [19 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Oxford Vaccine Group, , University of Oxford, ; Oxford, UK
                [20 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Medawar Building, , University of Oxford, ; Oxford, UK
                [21 ]GRID grid.31147.30, ISNI 0000 0001 2208 0118, National Institute for Public Health and Environment, ; Bilthoven, Netherlands
                [22 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Nuffield Department of Medicine, , University of Oxford, ; Oxford, UK
                [23 ]GRID grid.271308.f, ISNI 0000 0004 5909 016X, Immunisation and Countermeasures Division, National Infections Service, , Public Health England, ; England, UK
                [24 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Experimental Medicine Division, , University of Oxford, ; Oxford, UK
                [25 ]GRID grid.9122.8, ISNI 0000 0001 2163 2777, University of Hannover, ; Hannover, Germany
                [26 ]GRID grid.271308.f, ISNI 0000 0004 5909 016X, Public Health England, ; England, UK
                [27 ]GRID grid.7445.2, ISNI 0000 0001 2113 8111, Imperial College London, ; London, UK
                [28 ]GRID grid.83440.3b, ISNI 0000000121901201, University College London, ; London, UK
                [29 ]GRID grid.17703.32, ISNI 0000000405980095, International Agency for Research on Cancer, ; Lyon, France
                [30 ]GRID grid.418021.e, ISNI 0000 0004 0535 8394, AIDS and Cancer Virus Program, , Frederick National Laboratory for Cancer Research, ; Frederick, MD USA
                Author information
                http://orcid.org/0000-0002-4502-2209
                http://orcid.org/0000-0002-7690-4925
                http://orcid.org/0000-0003-1938-5038
                http://orcid.org/0000-0003-1177-6923
                http://orcid.org/0000-0003-4919-2632
                http://orcid.org/0000-0002-8925-8280
                http://orcid.org/0000-0002-5012-4162
                http://orcid.org/0000-0002-0616-6963
                Article
                29307
                10.1038/s41467-022-29307-3
                8983701
                35383168
                fdf37ded-079a-43b2-9e51-465b16ae7dbd
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 June 2020
                : 4 March 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/100004440, Wellcome Trust (Wellcome);
                Award ID: 106289/Z/14/Z
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                infectious diseases,epidemiology,genetics research
                Uncategorized
                infectious diseases, epidemiology, genetics research

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