We anticipate that our approach to constructing a robust GPS predictor of obesity will generalize across a range of common diseases, raising both important opportunities and potential challenges for clinical medicine. First, the cohorts studied here were of European ancestry – future studies are needed to extend this approach across additional ancestral background and ensure equitable implementation into clinical practice. Second, rare monogenic mutations for conditions such as obesity can sometimes be treated by precise targeting of the perturbed pathway (Kuhnen et al., 2016). Whether polygenic risk can be disaggregated into driving pathways within each individual in a similar fashion remains uncertain (Khera and Kathiresan, 2017). Lastly, additional work is needed to optimize genetic risk disclosure and to test whether this disclosure can improve disease prevention or treatment.
