Fig. 1

Schematic overview of the study design. We extracted preprocessed brain imaging data provided by ABCD and UKB teams, which includes three macrostructural metrics (CA, cortical area; CT, cortical thickness; CV, cortical volume) at each of the 34 bilateral cortical regions, two microstructural metrics (FA, fractional anisotropy; MD, mean diffusivity) at each of the 10 major white matter tracts, and volume at each of seven subcortical structures (SV, subcortical volume). Polygenic risk scores (PRSs) for Alzheimer’s disease (AD) were calculated for each participant using the clumping and thresholding method at eight p-value thresholds for SNP selection. For ABCD and UKB populations, PRSs were based on GWAS data reported previously [6, 7]. We used linear mixed effect models to estimate the association of each brain structure phenotype with each of eight AD PRS in children and adults (age distribution: 9–11 in ABCD, 46–82 in UKB), controlled for multiple comparisons at false discovery rate = 5%. The Manhattan plot is based on a prior published AD GWAS summary data [6] downloaded from www.ebi.ac.uk/gwas/downloads/summary-statistics (under accession GCST90012877) and for illustrative use only. Abbreviations: GM, gray matter; WM, white matter; GWAS, genome-wide association study; ABCD, Adolescent Brain Cognitive Development Study; UKB, UK Biobank