Generalisability of Results from UK Biobank: Comparison With a Pooling of 18 Cohort Studies

Abstract Background The UK Biobank cohort study has become a much-utilised and influential scientific resource. With a primary goal of understanding disease aetiology, the low response to the original survey of 5.5% has, however, led to debate as to the generalisability of these findings. We therefore compared risk factor–disease estimations in UK Biobank with those from 18 nationally representative studies with conventional response rates. Methods We used individual-level baseline data from UK Biobank (N=502,655) and a pooling of data from the Health Surveys for England (HSE) and the Scottish Health Surveys (SHS), comprising 18 studies and 89,895 individuals (mean response rate 68%). Both study populations were aged 40-69 years at study induction and linked to national cause-specific mortality registries. Findings Despite a typically more favourable risk factor profile and lower mortality rates in UK Biobank participants relative to the HSE-SHS consortium, risk factors–endpoints associations were directionally consistent between studies, albeit with some heterogeneity in magnitude. For instance, for cardiovascular disease mortality, the age- and sex-adjusted hazard ratio (95% confidence interval) for ever having smoked cigarettes (versus never) was 2.04 (1.87, 2.24) in UK Biobank and 1.99 (1.78, 2.23) in HSE-SHS, yielding a ratio of hazard ratios close to unity (1.02, 0.88, 1.19; p-value 0.76). For hypertension (versus none), corresponding results were again in same direction but with a lower effect size in UK Biobank (1.89; 1.69, 2.11) than in HSE-SHS (2.56; 2.20, 2.98), producing a ratio of hazard ratios below unity (0.74; 0.62, 0.89; p-value 0.001). A similar pattern of observations were made for risk factors (smoking, obesity, educational attainment, and physical stature) in relation to different cancer presentations and suicide whereby the ratios of hazard ratios ranged from 0.57 (0.40, 0.81) and 1.07 (0.42, 2.74). Interpretation Despite a low response rate, aetiological findings from UK Biobank appear to be generalisable to England and Scotland.