Human cortex surface area expanded 2000-fold relative to mice mainly in association areas. Prefrontal cortex disproportionately expanded versus non-human primates. Global surface area shows highest genetic correlations with frontal regions (rg 0.80-0.93). Global thickness correlates highest with fronto-parietal regions (rg 0.71-0.92). Occipital area has lowest genetic overlap with total surface area. Adjusting for global measures halves discoverable loci and drops heritability 25%. GWAS g+r yields 756 loci versus 393 for GWAS r due to global signals. 17q21.31 inversion loci strongly affect global surface area and prefrontal regions. Shared genes between global and prefrontal involve immune function and neurodevelopment. Network analysis confirms genetic module overlap strongest for prefrontal and global area. Genes like MAPT in 17q21.31 explain more variance in prefrontal than global area. LASSO selects global measures as key predictors for all regional phenotypes. Results replicate in independent child sample with diverse ancestry. Cancer/cell cycle pathways enrich only when retaining global signals. RPSA gene affects cortical thickness across most regions. Anterior-posterior gradient mirrors evolutionary cortical hierarchy.