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General and specific patterns of cortical gene expression as substrates of complex cognitive functioning

View ORCID ProfileJoanna E. Moodie, View ORCID ProfileSarah E. Harris, Mat A. Harris, Colin R. Buchanan, Gail Davies, Adele Taylor, Paul Redmond, David Liewald, View ORCID ProfileMaria del C Valdés Hernández, Susan Shenkin, View ORCID ProfileTom C. Russ, View ORCID ProfileSusana Muñoz Maniega, View ORCID ProfileMichelle Luciano, View ORCID ProfileJanie Corley, Aleks Stolicyn, Xueyi Shen, Douglas Steele, Gordon Waiter, Anca Sandu-Giuraniuc, Mark E. Bastin, View ORCID ProfileJoanna M. Wardlaw, View ORCID ProfileAndrew McIntosh, View ORCID ProfileHeather Whalley, Elliot M. Tucker-Drob, Ian J. Deary, Simon R. Cox
doi: https://doi.org/10.1101/2023.03.16.532915
Joanna E. Moodie
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
2Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
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  • For correspondence: Joanna.moodie@ed.ac.uk simon.cox@ed.ac.uk
Sarah E. Harris
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
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Mat A. Harris
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
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Colin R. Buchanan
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
2Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
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Gail Davies
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
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Adele Taylor
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
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Paul Redmond
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
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David Liewald
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
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Maria del C Valdés Hernández
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
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  • ORCID record for Maria del C Valdés Hernández
Susan Shenkin
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
4Ageing and Health Research Group, Usher Institute, University of Edinburgh, UK
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Tom C. Russ
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
5Alzheimer Scotland Dementia Research Centre, University of Edinburgh, UK
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Susana Muñoz Maniega
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
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Michelle Luciano
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
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Janie Corley
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
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Aleks Stolicyn
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
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Xueyi Shen
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
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Douglas Steele
2Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
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Gordon Waiter
2Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
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Anca Sandu-Giuraniuc
2Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
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Mark E. Bastin
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
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Joanna M. Wardlaw
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
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Andrew McIntosh
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
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Heather Whalley
3Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, UK
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  • ORCID record for Heather Whalley
Elliot M. Tucker-Drob
6Department of Psychology, University of Texas, Austin, Texas 78712-0187, USA
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Ian J. Deary
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
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Simon R. Cox
1Lothian Birth Cohorts, Department of Psychology, The University of Edinburgh, UK
2Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Edinburgh, UK
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  • For correspondence: Joanna.moodie@ed.ac.uk simon.cox@ed.ac.uk
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Abstract

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, general rules may govern shared spatial fluctuations in expression across the genome. Such information would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. We find that the region-to-region variation in cortical expression profiles of 8235 genes covary across two major dimensions: cell-signalling/modification and transcription factors. These patterns are validated out-of-sample and across different data processing choices. Brain regions most strongly implicated in general cognitive ability (g; meta-analytic N = 40,929) have greater balance between downregulation and upregulation of both major components. We identify a further 34 genes as candidate substrates of g. The results provide insights into the cortical organisation of gene expression and its association with individual differences in cognitive functioning.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 17, 2023.
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General and specific patterns of cortical gene expression as substrates of complex cognitive functioning
Joanna E. Moodie, Sarah E. Harris, Mat A. Harris, Colin R. Buchanan, Gail Davies, Adele Taylor, Paul Redmond, David Liewald, Maria del C Valdés Hernández, Susan Shenkin, Tom C. Russ, Susana Muñoz Maniega, Michelle Luciano, Janie Corley, Aleks Stolicyn, Xueyi Shen, Douglas Steele, Gordon Waiter, Anca Sandu-Giuraniuc, Mark E. Bastin, Joanna M. Wardlaw, Andrew McIntosh, Heather Whalley, Elliot M. Tucker-Drob, Ian J. Deary, Simon R. Cox
bioRxiv 2023.03.16.532915; doi: https://doi.org/10.1101/2023.03.16.532915
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General and specific patterns of cortical gene expression as substrates of complex cognitive functioning
Joanna E. Moodie, Sarah E. Harris, Mat A. Harris, Colin R. Buchanan, Gail Davies, Adele Taylor, Paul Redmond, David Liewald, Maria del C Valdés Hernández, Susan Shenkin, Tom C. Russ, Susana Muñoz Maniega, Michelle Luciano, Janie Corley, Aleks Stolicyn, Xueyi Shen, Douglas Steele, Gordon Waiter, Anca Sandu-Giuraniuc, Mark E. Bastin, Joanna M. Wardlaw, Andrew McIntosh, Heather Whalley, Elliot M. Tucker-Drob, Ian J. Deary, Simon R. Cox
bioRxiv 2023.03.16.532915; doi: https://doi.org/10.1101/2023.03.16.532915

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