Population Neuroscience: Understanding Concepts of Generalizability and Transportability and Their Application to Improving the Public's Health.

In population neuroscience, samples are not often selected with equal or known probability from an underlying population of interest; in other words, samples are not often formally representative of a specified underlying population. This chapter provides an overview of an epidemiological approach to considering the implications of selective participation on the value of our results for population health. We discuss definitions of generalizability and transportability, given the growing recognition that generalizability and transportability are central for interpreting data that are aiming to be population-based. We provide evidence that differences in the prevalence of effect measure modifiers between a study sample and a target population will lead to a lack of generalizability and transportability. We provide an example of an association between a poly-genetic risk score and depression, showing how an internally valid association can differ based on the prevalence of effect measure modifiers. We show that when estimating associations, inferences from a study sample to a population can depend on clearly defining a target population. Given that representative sampling from explicitly defined target populations may not be feasible or realistic in many situations, especially given the sample sizes needed for statistical power for many exposures of interest (and especially when interactions are being tested), researchers should be well versed in tools available to enhance the interpretability of samples regarding target populations.