Identification of host-pathogen-disease relationships using a scalable Multiplex Serology platform in UK Biobank

<jats:p>Background: Certain infectious agents are recognised causes of cancer and potentially other chronic diseases. Identifying associations and understanding pathological mechanisms involving infectious agents and subsequent chronic disease risk will be possible through measuring exposure to multiple infectious agents in large-scale prospective cohorts such as UK Biobank. Methods: Following expert consensus we designed a Multiplex Serology platform capable of simultaneously measuring quantitative antibody responses against 45 antigens from 20 infectious agents implicated in non-communicable diseases, including human herpes, hepatitis, polyoma, papilloma, and retroviruses, as well as <jats:italic>Chlamydia trachomatis</jats:italic>, <jats:italic>Helicobacter pylori</jats:italic> and <jats:italic>Toxoplasma gondii</jats:italic>. This panel was assayed in a random subset of UK Biobank participants (n=9,695) to test associations between infectious agents and recognised demographic and genetic risk factors and disease outcomes. Findings: Seroprevalence estimates for each infectious agent were consistent with those expected from the literature. The data confirmed epidemiological associations of infectious agent antibody responses with sociodemographic characteristics (e.g. lifetime sexual partners with <jats:italic>C. trachomatis</jats:italic>; <jats:italic>P</jats:italic>=1.8x10<jats:sup>-149</jats:sup>), genetic variants (e.g. rs6927022 with Epstein-Barr virus (EBV) EBNA1 antibodies, <jats:italic>P</jats:italic>=9.5x10<jats:sup>-91</jats:sup>) and disease outcomes including human papillomavirus-16 seropositivity and cervical intraepithelial neoplasia (odds ratio 2.28, 95% confidence interval 1.38-3.63), and quantitative EBV viral capsid antigen responses and multiple sclerosis through genetic correlation (MHC rG=0.30, <jats:italic>P</jats:italic>=0.01). Interpretation: This dataset, intended as a pilot study to demonstrate applicability of Multiplex Serology in epidemiological studies, is itself one of the largest studies to date covering diverse infectious agents in a prospective UK cohort including those traditionally under-represented in population cohorts such as human immunodeficiency virus-1 and <jats:italic>C. trachomatis</jats:italic>. Our results emphasise the validity of our Multiplex Serology approach in large-scale epidemiological studies opening up opportunities for improving our understanding of host-pathogen-disease relationships. These data are available to researchers interested in examining the relationship between infectious agents and human health.</jats:p>