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The genetic architecture of human cortical folding
- van der Meer, Dennis;
- Kaufmann, Tobias;
- Shadrin, Alexey A;
- Makowski, Carolina;
- Frei, Oleksandr;
- Roelfs, Daniel;
- Monereo-Sánchez, Jennifer;
- Linden, David EJ;
- Rokicki, Jaroslav;
- Alnæs, Dag;
- de Leeuw, Christiaan;
- Thompson, Wesley K;
- Loughnan, Robert;
- Fan, Chun Chieh;
- Westlye, Lars T;
- Andreassen, Ole A;
- Dale, Anders M
- et al.
Published Web Location
https://doi.org/10.1126/sciadv.abj9446Abstract
The folding of the human cerebral cortex is a highly genetically regulated process that allows for a much larger surface area to fit into the cranial vault and optimizes functional organization. Sulcal depth is a robust yet understudied measure of localized folding, previously associated with multiple neurodevelopmental disorders. Here, we report the first genome-wide association study of sulcal depth. Through the multivariate omnibus statistical test (MOSTest) applied to vertex-wise measures from 33,748 U.K. Biobank participants (mean age, 64.3 years; 52.0% female), we identified 856 genome-wide significant loci (P < 5 × 10−8). Comparisons with cortical thickness and surface area indicated that sulcal depth has higher locus yield, heritability, and effective sample size. There was a large amount of genetic overlap between these traits, with gene-based analyses indicating strong associations with neurodevelopmental processes. Our findings demonstrate sulcal depth is a promising neuroimaging phenotype that may enhance our understanding of cortical morphology.
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