Associations between biological ageing and the risk of, genetic susceptibility to, and life expectancy associated with rheumatoid arthritis: a secondary analysis of two observational studies

SummaryBackgroundRheumatoid arthritis is a chronic autoimmune disorder that affects life expectancy. Accelerated biological ageing is thought to be a major risk factor for age-related diseases, but its role in rheumatoid arthritis remains uncertain. We aimed to assess the associations between biological ageing and risk of rheumatoid arthritis and genetic susceptibility to the disease. We also aimed to assess the effect of biological ageing on the life expectancy of people with rheumatoid arthritis.MethodsWe calculated the chronological age-adjusted biological age—by both the Klemera-Doubal method (KDMAge) and phenotypic age (PhenoAge)—as a surrogate measure for biological ageing in participants from the US National Health and Nutrition Examination Survey (NHANES) and UK Biobank study. KDMAge or PhenoAge acceleration was defined as the residual of the regression of KDMAge or PhenoAge based on chronological age. Participants with accelerated biological ageing had KDMAge or PhenoAge acceleration values greater than 0, whereas those without accelerated ageing had values less than or equal to 0. We did cross-sectional analyses to assess the association between biological ageing and prevalent rheumatoid arthritis in both cohorts and prospective analyses to assess the association between biological ageing and incident rheumatoid arthritis in the UK Biobank. Logistic regression and Cox proportional hazards models were used to analyse these associations. Polygenic risk scores were used to establish genetic susceptibility to rheumatoid arthritis and to analyse the interaction between biological ageing and genetic risk. We also assessed the association between life expectancy and biological ageing status in people with rheumatoid arthritis.FindingsIn the cross-sectional analyses, each 1-year increase in age-adjusted biological age was associated with an increase in the risk of rheumatoid arthritis of between 1% and 10%. In the NHANES, individuals with accelerated ageing had a higher risk of rheumatoid arthritis than non-accelerated ageing individuals, with odds ratios of 1·21 (95% CI 1·03–1·42; p=0·018) for KDMAge acceleration and 1·46 (1·26–1·69; pInterpretationAccelerated biological ageing could increase the risk of rheumatoid arthritis, especially among people with high genetic risk, and could reduce the life expectancy of people with rheumatoid arthritis. The identification of populations with accelerated biological ageing has important implications for reducing the risk of rheumatoid arthritis and of lowered life expectancy.FundingNational Natural Science Foundation of China.