PT  - JOURNAL ARTICLE
AU  - Dennis van der Meer
AU  - Tobias Kaufmann
AU  - Alexey A. Shadrin
AU  - Carolina Makowski
AU  - Oleksandr Frei
AU  - Daniel Roelfs
AU  - Jennifer Monereo Sánchez
AU  - David E.J. Linden
AU  - Jaroslav Rokicki
AU  - Christiaan de Leeuw
AU  - Wesley K. Thompson
AU  - Robert Loughnan
AU  - Chun Chieh Fan
AU  - Paul M. Thompson
AU  - Lars T. Westlye
AU  - Ole A. Andreassen
AU  - Anders M. Dale
TI  - The genetic architecture of human cortical folding
AID  - 10.1101/2021.01.13.426555
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.13.426555
4099  - http://biorxiv.org/content/early/2021/01/14/2021.01.13.426555.short
4100  - http://biorxiv.org/content/early/2021/01/14/2021.01.13.426555.full
AB  - 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 a range of neurodevelopmental disorders. Here, we report the first genome-wide association study of sulcal depth. Through the Multivariate Omnibus Statistical Test (MOSTest) applied to vertexwise measures from 33,748 participants of the UK Biobank (mean age 64.3 years, 52.0% female) we identified 856 genetic loci associated with sulcal depth at genome-wide significance (α=5×10-8). Comparison with two other measures of cortical morphology, cortical thickness and surface area, indicated that sulcal depth has higher yield in terms of loci discovered, higher heritability and higher effective sample size. There was a large amount of genetic overlap between the three traits, with gene-based analyses indicating strong associations with neurodevelopmental processes. Our findings demonstrate sulcal depth is a promising MRI phenotype that may enhance our understanding of human cortical morphology.Competing Interest StatementDr. de Leeuw is funded by Hoffman-La Roche. Dr. Andreassen has received speakers honorarium from Lundbeck, and is a consultant to HealthLytix. Dr. Dale is a Founder of and holds equity in CorTechs Labs, Inc, and serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc. and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by UCSD in accordance with its conflict of interest policies. The other authors declare no competing financial interests.