Dietary Factors and Rheumatoid Arthritis Risk in the UK Biobank

Background: RA is the most common inflammatory arthritis in the United Kingdom, contributing significantly to increased morbidity and mortality, particularly from cardiovascular diseases. Epidemiological evidence suggests that compared to occasional drinkers, moderate alcohol consumption may reduce RA risk compared to non-drinkers, and occasional drinking. Additionally, observational research highlights the potential for RA risk reduction through dietary modifications, though evidence on interactions between dietary and genetic factors remains limited, particularly in prospective cohort studies. Moreover, the mechanisms underlying potential differences in RA risk between men and women are not yet fully understood. This study aims to assess the associations between dietary factors, such as alcohol consumption and dietary patterns, and RA incidence within the UK Biobank cohort. A secondary objective is to evaluate the role of potential modifiers in the relationship between dietary factors and RA risk, including adherence to the Alternative Healthy Eating Index (AHEI), Townsend index, as well as age, sex, body mass index (BMI), smoking status, and physical activity. Additionally, interactions between dietary factors and genetic profiles in relation to RA risk will be investigated. Research plan and methods: This study will utilize dietary and lifestyle data from the UK Biobank, a cohort that recruited over 500,000 adults from 2006 to 2010, and linked hospital records to identify incident RA cases. Cox proportional hazards regression models will be employed to examine associations between dietary factors and RA incidence, adjusting for relevant confounders. Potential effect modifiers such as age, sex, AHEI score, Townsend index, BMI, smoking status, physical activity, and gene-diet interactions will be analyzed by including interaction terms in the Cox models. Causal mediation analysis will further clarify the role of potential mediators. Additionally, inflammatory and immune-related factors, metabolic profile, and genetic susceptibility will be assessed to explore their contributions to RA risk.