Retrospective studies, in which well-characterized individuals with a particular disease are compared with control individuals without the disease, can be a highly efficient way of assessing the relevance of potential risk factors. Such studies have been a particularly productive source of evidence about genetic associations with health outcomes, especially after it was recognized that these studies need to involve large numbers of individuals (with appropriate allowance for multiple testing) to detect the weak associations that exist with most genetic variants. However, because the onset and prodrome of disease can affect risk factor levels (eg, myocardial infarction may lead to smoking cessation, cognitive decline may result in reduced physical activity), retrospective studies typically provide less reliable evidence about associations with modifiable risk factors. Moreover, because each such study is focused on individuals with some particular condition, it cannot inform about the relevance of a particular risk factor for many different conditions.
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Chen Z, Emberson J, Collins R. Strategic Need for Large Prospective Studies in Different Populations. JAMA. Published online December 09, 2019. doi:10.1001/jama.2019.19736
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