Abstract
Introduction Little is understood about the dynamic interplay between brain morphology and cognitive ability across the life course. Additionally, most existing research has focused on global morphology measures such as estimated total intracranial volume, mean thickness, and total surface area.
Methods Mendelian randomization was used to estimate the bidirectional effects between cognitive ability, global and regional measures of cortical thickness and surface area, estimated total intracranial volume, total white matter, and the volume of subcortical structures (N=37,864). Analyses were stratified for developmental periods (childhood, early adulthood, mid-to-late adulthood; age range: 8-81 years).
Results The earliest effects were observed in childhood and early adulthood in the frontoparietal lobes. A bidirectional relationship was identified between higher cognitive ability, larger estimated total intracranial volume (childhood, mid-to-late adulthood) and total surface area (all life stages). A thicker posterior cingulate cortex and a larger surface area in the caudal middle frontal cortex and temporal pole were associated with greater cognitive ability. Contrary, a thicker temporal pole was associated with lower cognitive ability.
Discussion Stable effects of cognitive ability on brain morphology across the life course suggests that childhood is potentially an important window for intervention.
Competing Interest Statement
Dr Banaschewski served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire. He received conference support or speaker's fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire and Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. Dr Poustka served in an advisory or consultancy role for Roche and Viforpharm and received speaker's fee by Shire. She received royalties from Hogrefe, Kohlhammer and Schattauer. The present work is unrelated to the above grants and relationships.
Funding Statement
RKL was supported by a Wellcome Trust PhD studentship (Grant ref: 215193/Z18/Z). ELA was supported by a fellowship from the UK Medical Research Council (MR/P014437/1). The Medical Research Council (MRC) and the University of Bristol support the MRC Integrative Epidemiology Unit [MC_UU_00011/1]. NMD was supported by a Norwegian Research Council Grant number 295989. YBS receives grant funding from the following: MRC, Wellcome Trust, NIHER, Templeton Foundation, Parkinson's UK, HQIP, Versus Arthritis, Dunhill Medical Trust, Gatsby Foundation, Kidney Research UK. LDH was funded by a Career Development Award from the UK Medical Research Council (MR/M020894/1). TJW is funded by Netherlands Organization for Health Research and Development (ZonMw) TOP project number 91211021. This research was supported by contract R01-HL105756-07 from the National Heart, Lung, and Blood Institute (NHLBI). CAMC is supported by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement No 707404 and grant agreement No 848158 (EarlyCause Project). YBS receives grant funding from the following: MRC, Wellcome Trust, NIHER, Templeton Foundation, Parkinson's UK, HQIP, Versus Arthritis, Dunhill Medical Trust, Gatsby Foundation, Kidney Research UK.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
UK Biobank is approved by the National Health Service National Research Ethics Service (ref 11/NW/0382; UK Biobank application number 48970. Ethics approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees and informed consent for the use of data collected via questionnaires and clinics was obtained from participants. In Generation R, all study protocols and measurements assessed in each wave of data collection were approved by the Medical Ethical Committee (MEC 198.782/2001/31) of the Erasmus MC, University Medical Center Rotterdam. The IMAGEN study was approved by the institutional ethics committee of Kings College London, University of Nottingham, Trinity College Dublin, University of Heidelberg, Technische Universitat Dresden, Commissariat a l Energie Atomique et aux Energies Alternatives, and University Medical Center at the University of Hamburg in accordance with the Declaration of Helsinki. The UCSD IRB approved all data collection protocols for ABCD. IRB number: 160091. All analyses in this study used de-identified data, therefore no additional IRB approval was required.
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Data Availability
The ENIGMA consortium MRI summary measures from genetic association analyses of estimated total intracranial volume, subcortical structures, as well as cortical thickness were requested online. The ABCD Study data are openly available to qualified researchers for free (https://nda.nih.gov/abcd/request-access). Requests for Generation R data should be directed toward the management team of the Generation R Study (secretariaat.genr@erasmusmc.nl), which has a protocol of approving data requests. For access to IMAGEN data, researchers may submit a request to the IMAGEN consortium (https://imagen-europe.com/resources/imagen-project-proposal/). ALSPAC details and data descriptions are available on their website (www.bristol.ac.uk/alspac/researchers/access), where applications for individual-level data can be made (managed access). UK Biobank data are available through a procedure described on their website (http://www.ukbiobank.ac.uk/using-the-resource/).
https://github.com/rskl92/intelligence_brain_morphology_bidirectional_MR