With large-scale retrospective studies and disease course trajectory data, PRS may help articulate longitudinal timelines relevant to phenotypic variation. For example, the apolipoprotein E4 (ApoE4) allele is the strongest genetic risk factor for late-onset Alzheimer’s disease with a large effect on cognitive decline among individuals in their 50s and 60s. It has no effect on educational attainment in youth, however, and greater resolution into genetic timelines will become increasingly available with larger studies and novel methods. By aggregating PRS with clinical features such as current health, family history, cognitive, and behavioral measures that predict disease in patients’ coming years of life, preventative trials can be more productive (102). Alzheimer’s disease, dementia with Lewy bodies, and Parkinson’s disease have symptomatic overlap with some diagnoses only confirmed post mortem. These three dementia disorders are genetically correlated, but some distinctive genetic signatures relating to each (103; 104) may provide granularity into differential diagnosis, enabling more rapid success in clinical trials through streamlining patient selection and reduced overall costs (105).
