Journal article

The genetic architecture of the human cerebral cortex

Katrina L Grasby, Neda Jahanshad, Jodie N Painter, Lucia Colodro-Conde, Janita Bralten, Derrek P Hibar, Penelope A Lind, Fabrizio Pizzagalli, Christopher RK Ching, Mary Agnes B McMahon, Natalia Shatokhina, Leo CP Zsembik, Sophia I Thomopoulos, Alyssa H Zhu, Lachlan T Strike, Ingrid Agartz, Saud Alhusaini, Marcio AA Almeida, Dag Alnaes, Inge K Amlien Show all

SCIENCE | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2020

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 tha..

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Grants

Awarded by National Institutes of Health (NIH) Big Data to Knowledge (BD2K) Initiative, a cross-NIH partnership


Awarded by National Health and Medical Research Council (NHMRC)


Awarded by NHMRC Senior Research Fellowship


Awarded by German Federal Ministry of Education and Science (BMBF)


Awarded by German Research Foundation (DFG)


Awarded by BMBF through the Integrated Network IntegraMent under the e:Med Program


Awarded by Swiss National Science Foundation


Awarded by European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (H2020)


Awarded by NIH


Awarded by Department of Defense ADNI


Awarded by Michael J. Fox Foundation (MJFF)


Awarded by NIA


Awarded by NLM


Awarded by Wellcome


Awarded by UK Medical Research Council (MRC)


Awarded by NHMRC


Awarded by HelseVest RHF


Awarded by Research Council of Norway



Funding Acknowledgements

This study was supported by U54 EB020403 from the National Institutes of Health (NIH) Big Data to Knowledge (BD2K) Initiative, a cross-NIH partnership. Additional support was provided by R01 MH116147, R01 MH1161671, P41 EB015922, RF1 AG051710, RF1 AG041915, R56 AG058854, R01 AG059874, R01 MH117601, the Michael J. Fox Foundation (MJFF; 14848), the Kavli Foundation, and National Health and Medical Research Council (NHMRC) Project Grant 1158127 (to S.E.M.). S.E.M. was funded by an NHMRC Senior Research Fellowship (APP1103623). K.L.G. was supported by APP1173025. L.C.-C. was supported by a QIMR Berghofer Fellowship. J.L.S. was supported by R01MH118349 and R00MH102357. The 1000BRAINS cohort thanks the Heinz Nixdorf Foundation (Germany) for generous support of the Heinz Nixdorf Recall Study, which is also supported by the German Federal Ministry of Education and Science (BMBF; FKZ 01EG940) and the German Research Foundation (DFG; ER 155/6-1). This work was further supported by the BMBF through the Integrated Network IntegraMent under the e:Med Program (01ZX1314A to S.Ci) and the Swiss National Science Foundation (156791 to S.Ci). The Initiative and Networking Fund of the Helmholtz Association supported S.Ca, the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (H2020) supported S.Ci (Human Brain Project SGA1, 720270) and supported S.Ca and S.Ci (Human Brain Project SGA2, 785907). The Alzheimer's Disease Neuroimaging Initiative (ADNI1 and ADNI2GO) was supported by NIH (U01 AG024904) and Department of Defense ADNI (W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from AbbVie; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche, Ltd., and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development, LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer, Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research provided funds to support ADNI clinical sites in Canada. Private sector contributions were facilitated by the Foundation for the National Institutes of Health (FNIH) (www.fnih.org).The grantee organization is the Northern California Institute for Research and Education, and the study was coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. Samples used in this study were from the National Centralized Repository for Alzheimer's Disease and Related Dementias, which received government support under a cooperative agreement grant (U24 AG21886) awarded by the NIA. Support for data analysis was provided by NLM R01 LM012535 and NIA R03 AG054936 (to K.N.). The UK Medical Research Council (MRC) and Wellcome (102215/2/13/2) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf).ALSPAC neuroimaging data were specifically funded by R01 MH085772 (to T.P.r r ). GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America), with support from 23andMe. Data and sample collection by the Australian Schizophrenia Research Bank (ASRB) were supported by the Australian NHMRC, the Pratt Foundation, Ramsay Health Care, and the Viertel Charitable Foundation. The ASRB was also supported by the Schizophrenia Research Institute (Australia), with infrastructure funding from NSW Health and the Macquarie Group Foundation. DNA analysis was supported by the Neurobehavioral Genetics Unit, with funding from NSW Health and the NHMRC Project Grants (1067137, 1147644, 1051672). M.C. was supported by a NHMRC Senior Research Fellowship (1121474). C.P. was supported by a NHMRC Senior Principal Research Fellowship (628386 and 1105825). BETULA was supported by a Wallenberg Scholar grant from the Knut and Alice Wallenberg Foundation and a grant from Torsten and Ragnar Soderbergs Foundation to L.N., HelseVest RHF (911554 to S.L.H.), grants from the Bergen Research Foundation and the University of Bergen to S.L.H., grants from the Dr Einar Martens Fund and the K.G. Jebsen Foundation to S.L.H. and V.M.S., and the Research Council of Norway (177458/V 50 to T.E. and 204966/F 20 to L.T.W.). Nijmegen's BIG resource is part of Cognomics, a joint initiative by researchers of the Donders Centre for Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the Radboud University Medical Center, and the Max Planck LLC; Neuralstem; Taisho; Heptares; Pfizer; Sound Pharma; Luye Pharma; Takeda; and Regeneron. N.H. is a stockholder of Siemens AG, Erlangen, Germany. R.B. has received travel grants and speaker honoraria from Bayer Healthcare, AG. R.L.B. is a paid consultant for Roche.