A Phenome-Wide Association Study (Phewas) Of  Late Onset Alzheimer Disease Genetic Risk in Children of European Ancestry at Middle Childhood: Results From the ABCD Study

Genetic risk for Late Onset Alzheimer disease (AD) has been associated with lower cognition and smaller hippocampal volume in healthy young adults. However, it remains unclear whether these and other associations are present during childhood. Using data from 5,556 genomically-confirmed European ancestry youth who completed the baseline session of the ongoing the Adolescent Brain Cognitive Development Study SM (ABCD Study®), our phenome-wide association study estimating associations between indices of genetic risk for late-onset AD (n = 4; AD polygenic risk scores (PRS), APOE rs429358 genotype, AD PRS with the APOE region removed (AD PRS−APOE ), and an interaction between AD PRS−APOE and APOE genotype) and 1,687 psychosocial, behavioral, and neural phenotypes revealed no significant associations after correction for multiple testing (all ps > 0.0002; all p fdr >0.07). These data suggest that AD genetic risk may not phenotypically manifest during middle-childhood or that effects are smaller than this sample is powered to detect.