Objective: To detect the association between regional adiposity distribution and the incidence of seven autoimmune diseases (ADs) in UK Biobank cohort and Mendelian randomization (MR) analyses.

Methods: We used Cox models to evaluate the associations between seven adiposity distribution measures and seven ADs (systemic lupus erythematosus [SLE], seropositive rheumatoid arthritis [PRA], psoriasis [PSO], multiple sclerosis [MS], myasthenia gravis [MG], Crohn's disease [CD] and ulcerative colitis [UC]) in cohort studies. In the MR analyses, we used the inverse variance-weighted MR method to estimate causal effects between adiposity distribution and obesity-related ADs in the cohort.

Results: In the cohort study, PSO, MG, CD, and female UC were associated with almost all types of adiposity distribution; PRA and male UC were associated with central adiposity distribution; SLE and MS were found to be not associated with any types of obesity. Almost all adiposity distribution were certified in MR as an exposure to PSO, MG and PRA.

Conclusions: Adiposity, despite its distribution, are associated with an increased risk of PSO and MG, and central adiposity distribution is robustly associated with the increased risk of PRA, indicating that lifestyle interventions aimed at obesity contribute to preventing ADs. Key Points • Body mass index (BMI) was a risk factor for several autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriasis (PSO), multiple sclerosis (MS) and inflammatory bowel disease (IBD). However, obesity as a heterogeneous and complex condition and that regional fat mass has obviously differential contributions to the development of obesity-related diseases. • We revealed that all types of adiposity distribution, whether general, central or peripheral, were associated with an increased risk of psoriasis and myasthenia gravis, and central adiposity distribution was robustly associated with the increased risk of seropositive rheumatoid arthritis. • Our findings indicated that lifestyle interventions aimed at individuals with obesity might contribute to preventing autoimmune diseases.