Autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis/psoriatic arthritis, ankylosing spondylitis, Sjögren’s syndrome, systemic sclerosis, celiac disease, inflammatory myopathies, and myasthenia gravis cause substantial morbidity and mortality worldwide. Their pathogenesis involves complex interactions between polygenic susceptibility, immune dysregulation, and environmental and lifestyle exposures. Although previous studies have identified risk loci and immune pathways, as well as associations between inflammatory blood biomarkers and disease activity, most biomarkers lack disease specificity, and the causal pathways linking genetic risk, intermediate phenotypes, and environmental modifiers remain unclear.
This project will leverage the large-scale, deeply phenotyped UK Biobank cohort to integrate genomic data, routine blood biomarkers, and detailed epidemiological information to elucidate the genetic architecture and epidemiological determinants of autoimmune diseases. We aim to characterise shared versus disease-specific genetic and biomarker profiles, clarify how genetic risk influences disease through alterations in blood biomarkers, and examine cross-disease similarities and differences. We will further assess the interplay between genetic predisposition, biomarker levels, and environmental or lifestyle factors such as diet, activity, sleep, medication use, pollution exposure, and socioeconomic status. By disentangling these relationships, the study will provide mechanistic insights and inform the development of interpretable, transferable risk stratification frameworks for early identification of high-risk individuals and personalised management strategies.