The genetic architecture of human cortical folding

Dennis Van Der Meer, Tobias Kaufmann, Alexey A. Shadrin, Carolina Makowski, Oleksandr Frei, Daniel Roelfs, Jennifer Monereo-Sánchez, David E.J. Linden, Jaroslav Rokicki, Dag Alnæs, Christiaan De Leeuw, Wesley K. Thompson, Robert Loughnan, Chun Chieh Fan, Lars T. Westlye, Ole A. Andreassen, Anders M. Dale

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Article numbereabj9446
Pages (from-to)1-9
Number of pages9
JournalScience advances
Issue number51
Early online date15 Dec 2021
Publication statusPublished - 17 Dec 2021

Bibliographical note

Funding Information:
The authors were funded by the Research Council of Norway (276082, 213837, 223273, 204966/F20, 229129, 249795/F20, 225989, 248778, 249795, 298646, and 300767), the South-Eastern Norway Regional Health Authority (2013-123, 2014-097, 2015-073, 2016-064, 2017-004, and 2019-101), Stiftelsen Kristian Gerhard Jebsen (SKGJ-Med-008), the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC Starting Grant, grant agreement no. 802998), ERA-Net Cofund through the ERA PerMed project "Implement," and the National Institutes of Health (R01MH100351, R01GM104400, U24DA055330, R01MH111359, and U24DA041123; principal investigator: A.M.D.).

Publisher Copyright:
© 2021 American Association for the Advancement of Science. All rights reserved.


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