The Whitehall II study: A Core Resource for Ageing Research

尽管老年痴呆症和心血管疾病等特定年龄慢性病的发病率有所下降，但由于人口老龄化和预期寿命延长，疾病负担继续上升。世卫组织审查、NICE指南和柳叶刀委员会强调了早期预防的重要性；如果我们能够确定最强的可改变的风险和保护因素，并排除虚假联系，那么通过瞄准中年因素来预防痴呆症和其他与年龄相关的疾病是有很大范围的。白厅II研究在研究界被广泛认为是一种独特的流行病学资源。作为一项关于老龄化的研究，它有几个特殊的特点：35岁的年轻基线捕捉成年早期的暴露，30年来有7个临床接触者的纵向设计，以及参与者的出色留存。WhiteHall II生物库包括33万份储存的血液、尿液和头发样本，我们的临床检查数据涵盖了10,000名英国男性和女性的人体测量、血压、心电图、一系列身体和认知功能测试以及全面的问卷测量。通过基因分型、代谢组学和蛋白质组学分析丰富了数据。所有参与者都被链接到电子健康记录。在赠款期间，通过相关数据确定的痴呆症和心脏代谢多发病的累计病例数量将超过1000例，中风病例将超过700例。我们的基础设施提案的首要目标是最大限度地发挥白厅二号作为科学发现和复制来源的潜力。这一资源将有助于我们对各种年龄相关疾病的病因和预后的了解，并将为预防提供信息。我们在将中年风险和保护因素与老龄化结果联系起来的科学框架内提供了范例假设，并强调了白厅II作为利益相关者资源的潜力，这些利益相关者包括学术界、卫生保健和政策制定者、资助者、患者、普通公众/慈善机构/患者倡导团体以及来自行业的研究人员。2018年至2023年的具体目标是：(1)确保可持续长期生物样本/数据存储的安排和今后研究的便利；(2)通过每年更新与电子健康记录的联系，丰富数据集；(3)确保有机会重新联系参与者，以便进一步收集数据；(4)通过更新数据共享机制，向更广泛的国家和国际研究界推广这一队列。我们是第一个由MRC资助的大规模队列研究，将我们与英国数据服务中心在研究期间收集的临床测量和问卷的去识别和整理数据存储起来，供世界各地的研究人员使用，并同样提供可用的生物样本供未来使用。

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.