Consistent with previous longitudinal studies (11, 17, 46), we observed strong age-related trends in prevalence, with AUBs peaking/plateauing in young adulthood. These trends were stable across cohorts separated by continents and decades, despite substantial differences in environments and study designs. Genetic associations with these trajectories, on the other hand, were highly variable, with the meta-analysis I2 statistics indicating that most of the variability in effect sizes for the PGSs was due to between-cohort heterogeneity (47). This highlights an ongoing challenge in utilizing results from GWASs, in which the hundreds of AUB-related genes identified through enormous, pooled samples are still only able to account for a small fraction of the known heritability of AUBs (4, 5), likely due to inter-individual variability in the specific causal genes and processes (45). Despite focusing on AUB dimensions defined with a bottom-up strategy based on their genetic architecture (26), between-sample heterogeneity remained high in our study.
