Towards a Better Understanding of the Genetics of the Human Cortical Folding

The folding of the human cerebral cortex, partly influenced by genetics, allows a large cortex surface area to fit efficiently within the limited skull space. Understanding folding shapes is limited given their wide variability, and identifying them is difficult. Here, we report the first genomic association study on a comprehensive representation of folding patterns. Via a multivariate statistical test applied to latent spaces generated by contrastive learning on 18,118 UKBioBank subjects (mean age, 62.5 years; 47.0% male), we identified in the orbitofrontal cortical region (OFC), respectively in the left and the right hemispheres, 15 and 11 loci (p < 5 × 10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−8</sup>), 11 and 5 genes (p < 2 × 10<sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">−6</sup>) related to brain folding. Finally, we introduce a method for interpreting genetic associations in terms of folding shapes. These findings pave the way for future research to map cortical folding patterns to genetic factors.