Junjiao Feng, Qingjing Jia, Dekang Wang, Feng Liu
Executive functions (EFs) are heritable higher‑order cognitive abilities, with a common factor (cEF) capturing shared variance across tasks. Whether early brain growth contributes to adult EF (and through which pathways) remains unclear. Using GWAS summary statistics, we applied linkage disequilibrium score regression, bidirectional two-sample Mendelian randomization (MR), and multivariable MR to investigate the genetically predicted influence of infant head circumference (HC) on adult cEF and the mediating role of cortical morphology. Infant HC, but not birth HC, showed a significant positive genetic correlation and a unidirectional genetically predicted effect on adult cEF. Total and regional cortical surface area (SA) in frontal, cingulate, and temporal regions exhibited significant genetic correlations and genetically predicted effects on adult cEF, with MVMR confirming that these regional effects remained significant after mutual adjustment. Infant HC showed strong genetic correlations and directional associations with the SA of these cEF‑related regions. Two‑step MR mediation analysis indicated that total and regional SA (anterior cingulate, superior frontal, superior temporal) are consistent with a partial mediating role in the genetically informed pathway from infant HC to adult cEF. Reverse mediation analyses further suggested a similar mediating role for infant HC in the pathway from cortical SA to adult cEF. Together, these results point to bidirectional mediation between infant HC and cortical SA, supporting a genetic‑developmental pathway in which early-life HC and cortical structure interact to shape lifelong executive capacity.