Because UK Biobank participants are, on average, more health-conscious than the general population, this cohort is not the best for estimation of generalizable prevalence or incidence rates of disease (although some health-related characteristics of the UK Biobank cohort, such as the prevalence of self-reported pain, have previously been shown to be similar to those of the national population (22)). In order for a cohort study to produce generalizable associations of exposures with disease, it is important that sufficiently large numbers of individuals with different levels of exposures be investigated with high internal validity (23–26). Indeed, if one were interested in investigating the association of ethnicity with subsequent disease risk, the most appropriate study design would be to recruit a large number of people from different ethnic backgrounds rather than have a representative, largely white population. Because UK Biobank is primarily designed for investigating exposure-disease associations, the lack of representativeness should not be regarded as a limitation (27, 28). As with all observational studies, it is incumbent upon researchers to acknowledge potential sources of bias that might affect the generalizability of
