The Whitehall II study: A core resource for ageing research

High quality and reproducibility in science cannot be achieved without a robust study design and high-quality data. The 37-year follow-up of 10,308 Whitehall participants from early midlife to old age with 8 clinical examinations, linked electronic health data and a biorepository which includes over 360,000 stored blood, urine, and hair samples is a unique resource for studying ageing and factors that affect the development and progression of chronic conditions, such as Alzheimer's disease and other dementias, cardiometabolic diseases, and multimorbidity.

To maximise the potential of Whitehall as a source of scientific discovery and replication and in accordance with recommendations from the MRC, we propose a cost-effective infrastructure that consists of an accessible biorepository and continued update of health outcomes of Whitehall participants via linkage to health records. Accordingly, we seek MRC funding for costs arising from biosample storage, data extraction services from national registers, and employment of staff to maintain the bioresource, facilitate biosample/data selection and transfers to collaborators; to update and process linked electronic health record data; to manage data sharing with the wider research community ensuring research governance requirements are met; and to curate new data for release to Dementia Platform UK ensuring that the most updated data and derived variables are fully documented and deidentified prior to release. As recommended by the MRC, this proposal does not request support for data analysis or further clinical examinations.

With continued infrastructure support, Whitehall resource will uniquely contribute to research aimed at understanding healthy ageing and age-related conditions, and continue to inform prevention, clinical guidelines and policy.

We seek MRC support for the Whitehall II study to ensure sustainable long-term biosample/data storage and ease of access; to enrich the dataset by annual update of linkage to electronic health records, including hospital admissions (diagnoses and treatments), cause of death, and use of mental health services (including dementia); to ensure the opportunity to re-contact participants for further data collection, and to continue and increase sharing of the data to the research community in the UK and elsewhere.

Whitehall II is a prospective cohort study of 10,308 women and men, aged 35 to 55 years at baseline in 1985-88, followed up with 8 repeated clinical examinations up to 2022. Biorepository includes 363,910 stored blood, urine, and hair samples; data from clinical examinations are anthropometry, blood pressure, electrocardiogram (ECG) and a range of physical and cognitive functional tests; genotyping from the Illumina Metabochip (200K SNPs) and the new Illumina Human Drug Core Array, which has a whole genome SNP scaffold with enhanced coverage with 200,000 custom markers in 4,500 drugged/druggable genes; serum NMR metabolomics profiling of 233 lipids, lipoproteins and metabolic intermediates; and proteomic profiling based on SOMAScan multiplexed assay for >7000 proteins.

During the grant period (by the end of 2026), the cumulative number of cases from updated electronic health records will be 2173 for dementia (including 1018 for Alzheimer's disease and 513 for vascular dementia), 2977 for coronary heart disease, 840 for strokes, 457 for liver disease, 3262 for cancers, and 6531 for deaths, providing future studies with sufficient power to detect a 1.25 to 1.4-fold relative risk for top compared to bottom tertile in midlife risk factors in relation to these age-related disease outcomes.