Comparison of risk factor associations in UK Biobank against representative, general population based studies with conventional response rates: prospective cohort study and individual participant meta-analysisBMJ 2020; 368 doi: https://doi.org/10.1136/bmj.m131 (Published 12 February 2020) Cite this as: BMJ 2020;368:m131
- G David Batty, professor of epidemiology1 2,
- Catharine R Gale, professor of cognitive epidemiology3 4,
- Mika Kivimäki, professor of social epidemiology1,
- Ian J Deary, professor of differential psychology4,
- Steven Bell, senior research associate in epidemiology5 6 7
- 1Department of Epidemiology and Public Health, University College London, London WC1E 6BT, UK
- 2School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR, USA
- 3MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
- 4Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, UK
- 5British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
- 6National Institute for Health Research Blood and Transplant Unit in Donor Health and Genomics at the University of Cambridge, Cambridge, UK
- 7Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
- Correspondence to: D Batty
- Accepted 16 December 2019
Objective To compare established associations between risk factors and mortality in UK Biobank, a study with an exceptionally low rate of response to its baseline survey, against those from representative studies that have conventional response rates.
Design Prospective cohort study alongside individual participant meta-analysis of other cohort studies.
Setting United Kingdom.
Participants Analytical sample of 499 701 people (response rate 5.5%) in analyses in UK Biobank; pooled data from the Health Surveys for England (HSE) and the Scottish Health Surveys (SHS), including 18 studies and 89 895 people (mean response rate 68%). Both study populations were linked to the same nationwide mortality registries, and the baseline age range was aligned at 40-69 years.
Main outcome measure Death from cardiovascular disease, selected malignancies, and suicide. To quantify the difference between hazard ratios in the two studies, a ratio of the hazard ratios was used with HSE-SHS as the referent.
Results Risk factor levels and mortality rates were typically more favourable in UK Biobank participants relative to the HSE-SHS consortium. For the associations between risk factors and mortality endpoints, however, close agreement was seen between studies. Based on 14 288 deaths during an average of 7.0 years of follow-up in UK Biobank and 7861 deaths over 10 years of mortality surveillance in HSE-SHS, for cardiovascular disease mortality, for instance, the age and sex adjusted hazard ratio for ever having smoked cigarettes (versus never) was 2.04 (95% confidence interval 1.87 to 2.24) in UK Biobank and 1.99 (1.78 to 2.23) in HSE-SHS, yielding a ratio of hazard ratios close to unity (1.02, 0.88 to 1.19). The overall pattern of agreement between studies was essentially unchanged when results were compared separately by sex and when baseline years and censoring dates were aligned.
Conclusion Despite a very low response rate, risk factor associations in the UK Biobank seem to be generalisable.
Contributions: GDB generated the idea for the study, formulated an analytical plan, and wrote the manuscript. CRG (UK Biobank) and SB (HSE-SHS) formulated an analytical plan and did all the data analyses. SB prepared the figures. All authors commented on an earlier version of the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. CRG had full access to UK Biobank data, and SB had full access to HSE-SHS data. GDB takes responsibility for the decision to submit the manuscript for publication. GDB, CRG, and SB are the guarantors.
Funding: GDB is supported by the UK Medical Research Council (MR/P023444/1) and the US National Institute on Aging (1R56AG052519-01; 1R01AG052519-01A1). MK is supported by the UK Medical Research Council (MR/R024227), the US National Institute on Aging (NIH) (R01AG056477), NordForsk, and the Academy of Finland (311492). CRG is supported by the UK Medical Research Council (MRC_MC_UU_12011/2 and MRC_MC_UP_A620_1015). SB is supported by the NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024), UK Medical Research Council (MR/L003120/1), British Heart Foundation (RG/13/13/30194), and NIHR Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust. There was no direct financial or material support for the work reported in the manuscript. The funders of the studies had no role in study design, data collection, data analysis, data interpretation, or report preparation.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; the authors have published papers using data from the studies featured in this manuscript (these counts are not mutually exclusive, such that selected publications involve more than one author from the present group and more than one of the datasets: GDB (8 UK Biobank; 38 HSE/SHS), CRG (28; 2), MK (4; 13), IJD (30; 0), and SB (9; 9)); IJD was responsible for the design of some of the cognitive function tests in the revised battery used in the imaging sessions in UK Biobank and is also a study participant; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: In UK Biobank, ethical approval for data collection was received from the North-West Multi-centre Research Ethics Committee and the research was carried out in accordance with the Declaration of Helsinki of the World Medical Association. In HSE-SHS, ethical approval for data collection was granted by the London Research Ethics Council or local research ethics councils. No additional ethical approval was required for the analyses of the data. Participants in both studies gave informed consent.
Data sharing: Data from UK Biobank (https://www.ukbiobank.ac.uk/) and the Health Surveys for England and the Scottish Health Surveys (https://data-archive.ac.uk/) are available to bona fide researchers on application. Part of this research has been conducted using the UK Biobank Resource under Application 10279.
Transparency: GDB affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Dissemination to participants and related patient and public communities: Findings will be disseminated via the media departments of the authors’ institutes. Results from UK Biobank are routinely disseminated to study participants via the study website and Twitter feed.
Pre-print deposition: medRxiv (https://www.medrxiv.org/content/10.1101/19004705v1).
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