Effect Sizes and Replicability in Longitudinal Studies of Brain-Phenotype Associations

Oregon Convention Center 

Several recent studies showed that thousands of study participants are required to improve the replicability of brain-phenotype associations because actual effect sizes are much smaller than those reported in smaller studies. Here, we perform a meta-analysis of brain volume associations with age using 63 longitudinal and cross-sectional magnetic resonance imaging studies (77,695 total scans) to show that studies with larger covariate variance have larger effect size estimates and that the longitudinal studies we examined have systematically larger standardized effect sizes than cross-sectional studies. Analyzing age effects on global and regional brain measures in the LBCC, we show that modifying longitudinal study design to increase between-subject variability and adding a single additional longitudinal measurement per subject improves effect sizes. However, evaluating these longitudinal sampling schemes on other phenotype-brain associations in the ABCD dataset shows that longitudinal studies can be detrimental to effect sizes. We integrate these empirical results with statistical theory to elucidate their meaning and establish when longitudinal designs improve replicability.