RT Journal Article
SR Electronic
T1 The genetic architecture of human cortical folding
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.13.426555
DO 10.1101/2021.01.13.426555
A1 Dennis van der Meer
A1 Tobias Kaufmann
A1 Alexey A. Shadrin
A1 Carolina Makowski
A1 Oleksandr Frei
A1 Daniel Roelfs
A1 Jennifer Monereo Sánchez
A1 David E.J. Linden
A1 Jaroslav Rokicki
A1 Christiaan de Leeuw
A1 Wesley K. Thompson
A1 Robert Loughnan
A1 Chun Chieh Fan
A1 Paul M. Thompson
A1 Lars T. Westlye
A1 Ole A. Andreassen
A1 Anders M. Dale
YR 2021
UL http://biorxiv.org/content/early/2021/01/14/2021.01.13.426555.abstract
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.