The immunogenetics of humoral response, utilising COVID-19 as a model (360G-Wellcome-228321_Z_23_Z)

Human genetic variation influences inter-individual immune responses. Throughout the COVID-19 pandemic, the UK Biobank (UKB) collected an array of serological data on subsets of participants both pre/post-vaccination, including up to 200,000 individuals. UKB also contains a wide range of anthropometric data, alongside various other key variables, such as social deprivation, age and immunosuppression, which are all known to influence immune responses. I will perform genome-wide association studies (GWAS) of vaccine-related outcomes, whilst understanding and carefully adjusting for potential confounding variables. My primary aim is to detect genomic regions associated with variable SARS-CoV-2 antibody titers following vaccine administration. Associations in known/novel loci and their pathways will be verified and validated via conducting allele-specific survival analyses, meta- analyses, further GWAS and through investigating COVID-19-related outcomes. Regions of interest will be fine mapped and where appropriate, the functional effect of variation will be determined, initially in silico. Relevant pathways could be targeted with adjuvants in order to upregulate post-vaccination antibody response, thus improving vaccine efficacy, and helping to tailor and improve the next generation of vaccine designs. Although this research will be conducted on COVID-19 related data, there is great scope for application to a wide range of vaccines targeting infectious and other diseases.