The Whitehall II study: A Core Resource for Ageing Research

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Despite declining age-specific rates of chronic conditions, such as dementia and cardiovascular disease, the burden of disease continues to rise due to population ageing and increase in life expectancy. WHO reviews, NICE guidelines and Lancet commission emphasise the importance of early prevention; there is major scope for preventing dementia and other age-related disease by targeting midlife factors, provided we can identify the strongest modifiable risk and protective factors and rule out spurious associations. The Whitehall II study is widely recognised in the research community as a unique epidemiological resource. It has several special characteristics as a study of ageing: a young baseline at 35 years of age capturing exposures in early adulthood, longitudinal design with seven clinic contacts over 30 years, and excellent retention of participants. Whitehall II biorepository includes >330k stored blood, urine, and hair samples and our data from clinical examinations cover anthropometry, blood pressure, electrocardiogram, a range of physical and cognitive functional tests and comprehensive questionnaire measurements for 10,000 British men and women. The data are enriched by genotyping, metabolomic and proteomic profiling. All participants have been linked to electronic health records. During the grant period, the cumulative number of cases ascertained via linked data will exceed 1000 for dementia and cardiometabolic multimorbidity and be over 700 for stroke. The overarching aim of our infrastructure proposal is to maximise the potential of Whitehall II as a source of scientific discovery and replication. This resource will uniquely contribute to our understanding on the aetiology and prognosis of various age-related conditions, and will inform prevention. We provide example hypotheses within a scientific framework linking midlife risk and protective factors to ageing outcomes and highlight the potential of Whitehall II as a resource for stakeholders, including the academic community, health care and policy makers, funders, patients, the general public/charities/patient advocacy groups, and researchers from industry. The specific objectives for years 2018 to 2023 are: (1) to ensure arrangements for sustainable long-term biosample/data storage and ease of access for future studies; (2) to enrich the dataset by annual updates of linkage to electronic health records; (3) to ensure the opportunity to re-contact participants for further data collection; and (4) to promote the cohort to the wider national and international research communities by upgrading data sharing mechanisms. We are the first large-scale MRC-funded cohort study to deposit de-identified and curated data from the clinical measures and questionnaires collected during our study with the UK Data Service for use by researchers worldwide, and similarly to make available biosamples for future use.