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.

Abstract

Genetic risk for Late Onset Alzheimer Disease (AD) has been associated with lower cognition and smaller hippocampal volume in healthy young adults. However, whether these and other associations are present during childhood remains unclear. Using data from 5556 genomically-confirmed European ancestry youth who completed the baseline session of the ongoing the Adolescent Brain Cognitive Development^SM Study (ABCD Study®), our phenome-wide association study estimating associations between four indices of genetic risk for late-onset AD (i.e., 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 1687 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.