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The genetic architecture of the human cerebral cortex

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Abstract

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Original languageEnglish
Article numbereaay6690
Pages (from-to)1-14
Number of pages17
JournalScience
Volume367
Issue number6484
DOIs
Publication statusPublished - 20 Mar 2020

Bibliographical note

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Funding

FundersFunder number
Horizon 2020 Framework Programme
European Commission
National Human Genome Research InstituteU01HG004402
National Institute of Mental HealthR00MH102357, R00MH101367, R01MH085772, R01MH062873, R01MH094524, R01MH112180, K24MH094614, R01MH116147, R01MH078143, R01MH118349, R01MH111671, R01MH116948, T32MH067533, P50MH103222, R01MH079799, RC1MH089257, K08MH068540, R01MH058799, R01MH119243, K01MH099232, R01MH085646, U01MH108148, R01MH117601, R01MH078111, RC2MH089995, RC2MH089951, R01MH083824, R01MH081802, U24MH068457
National Institute on AgingR01AG033193, K08AG047903, R01AG023629, R01AG054076, P30AG062429, RF1AG051710, R01AG016495, R03AG046413, U24AG021886, U01AG024904, R01AG022381, U01AG049505, R01AG022982, T32AG058507, R01AG033040, RF1AG041915, R56AG058854, R01AG049607, R01AG018386, R01AG018384, R01AG059874, R03AG054936, K99AG054573, P30AG010129, R01AG015928, R01AG008122
UK Research and InnovationMR/N000390/1
???publication-publication-funding-organisation-not-added???047.017.043
National Heart, Lung, and Blood InstituteU01HL080295, R01HL085083, R01HL105756, R01HL120393, R01HL059367, R01HL070825, R01HL103612, R01HL087652, R01HL087641, U01HL130114, R01HL086694, R01HL084099
National Institute on Drug AbuseR01DA025109, R01DA018673, R01DA033369, RC2DA029475, R00DA023549, UG3DA047685, R01DA031579, R01DA027680
National Center for Research ResourcesU24RR025736, P41RR014075, M01RR001066, U24RR021992, S10RR023043, UL1RR025005, S10RR023401
National Institute of Biomedical Imaging and BioengineeringR01EB015611, P41EB015922, R01EB005846, R01EB000840, U54EB020403, R01EB006841
Biotechnology and Biological Sciences Research CouncilBB/F019394/1
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung156791
U.S. Department of Veterans AffairsI01CX000497
Seventh Framework Programme602768, 115916, 695313, 667375, 602805, 785907, 667302, 1302755, 720270, 643051, 1531491, 201413, 728018, 115300, 230374, 602450, 278948, 640643, 284167, 603016, 643417, 602633
National Health and Medical Research Council1022684, 350833, 1037746, 630434, 1105825, 389891, 630428, 1009064, 401184
National Institute of Child Health and Human DevelopmentR01HD050735, R01HD061414
???publication-publication-funding-organisation-not-added???16/ERCD/3797
NIH Office of the DirectorS10OD023696
National Center for Advancing Translational SciencesUL1TR000124, UL1TR001881, UL1TR000153
National Institute of Neurological Disorders and StrokeR01NS087541, R01NS017950, R01NS073134, R24NS092988, R01NS042867
National Institute of Diabetes and Digestive and Kidney DiseasesR01DK092127, P30DK063491
National Science Foundation1302755, 1531491
Wellcome Trust088324, 084730
Medical Research CouncilMR/L010305/1
Japan Society for the Promotion of Science19H05467, 18KT0022
???publication-publication-funding-organisation-not-added???P 13180
U.S. National Library of MedicineR01LM012535
National Institute of General Medical SciencesP20GM103472
Agence Nationale de la RechercheANR-12-SAMA-0004

    Cohort Studies

    • Netherlands Twin Register (NTR)

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