"Background: Increased life expectancy and decreased birth rates resulted in more elderly people and in a higher prevalence of chronic diseases and associated disability throughout the EU. However, evidence of genetic variants associated with increased risk of disability and of causal links between underlying diseases and disability is limited.Objectives: To identify women who are at higher risk of disability and to delineate potential causal pathways resulting in disability with a special focus on inflammatory response. Specific objectives are:1) To develop defined phenotypes of disability from different dimensions of the concept of disability.2) To evaluate the effect of selected sets of biomarkers or physical measurements as proxies for different biological pathways with disability phenotypes.3) To identify genetic variants associated with disability phenotypes.4) To estimate the magnitude of causal associations between levels of selected inflammatory markers and disability phenotypes based on the concept of Mendelian randomisation.Methods: Already existing data from the British Women’s Heart and Health Study, a large prospective cohort study in the UK, will be used for this project. Latent class analysis will be used to delineate distinct phenotypes of disability. Associations between disability and different sets of biomarkers as proxies for biological pathways will be estimated with structural equation models. Selected genetic variants will be tested for association with disability. Causal effects of inflammatory response on disability will be evaluated in a Mendelian randomisation analysis.Relevance: This project will contribute to a better understanding of the epidemiology of disability and will provide novel insights into biological mechanisms underlying different disability phenotypes in elderly women. Results may help to improve predictions of long-term effects and inform implementation of preventive measures and optimal treatment strategies."