Autoimmune diseases represent a significant source of morbidity and mortality and are a major financial burden to the economy. Evidence has emerged from cohort studies and animal models of disease of a link between viruses and many autoimmune conditions. The development of several promising vaccines and therapies targeting viral infection affords the tantalising possibility that new agents and existing antiviral treatments could be used to treat or even prevent autoimmune disease, and indeed some are already in Phase 1 clinical trials. However before embarking on large and expensive trials evaluating the effectiveness of such agents, the issue of whether viral pathogens trigger autoimmune disease needs to be established convincingly. The overall aim of this project is to investigate a possible causal link between six ubiquitous human viruses and the development of four autoimmune diseases using a statistical genetics methodology that is robust to confounding and reverse causality, and will be able to provide evidence in favour or against a role of viral infection in disease aetiology. Our approach involves finding genetic variants associated with antibody response to viral infection and determining whether the same variants also affect risk of autoimmune disease using a technique called Mendelian randomization. Should our results be consistent with a causal relationship, we expect that approaches aimed at controlling viral infection through vaccination, antiviral drugs or treatment with virus-specific T cell
infusions may become effective treatments or preventative strategies against autoimmune diseases in the future. Equally important, should we find no evidence for a causal relationship, then our results would suggest that expensive clinical trials involving anti-viral agents and/or vaccines to these pathogens are unlikely to succeed and shouldn’t be conducted- potentially saving hundreds of millions of dollars by avoiding costly studies likely to fail.