Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types

Stan L. W. Driessens, Anna A. Galakhova, Djai B. Heyer, Isabel J. Pieterse, René Wilbers, Eline J. Mertens, Femke Waleboer, Tim S. Heistek, Loet Coenen, Julia R. Meijer, Sander Idema, Philip C. Witt Hamer, David P. Noske, Christiaan P. J. Kock, Brian R. Lee, Kimberly Smith, Jonathan T. Ting, Ed S. Lein, Huibert D. Mansvelder and Natalia A. Goriounova ()
Additional contact information
Stan L. W. Driessens: Vrije Universiteit Amsterdam
Anna A. Galakhova: Vrije Universiteit Amsterdam
Djai B. Heyer: Vrije Universiteit Amsterdam
Isabel J. Pieterse: Vrije Universiteit Amsterdam
René Wilbers: Vrije Universiteit Amsterdam
Eline J. Mertens: Vrije Universiteit Amsterdam
Femke Waleboer: Vrije Universiteit Amsterdam
Tim S. Heistek: Vrije Universiteit Amsterdam
Loet Coenen: Vrije Universiteit Amsterdam
Julia R. Meijer: Vrije Universiteit Amsterdam
Sander Idema: Amsterdam UMC Location Vrije Universiteit Amsterdam
Philip C. Witt Hamer: Amsterdam UMC Location Vrije Universiteit Amsterdam
David P. Noske: Amsterdam UMC Location Vrije Universiteit Amsterdam
Christiaan P. J. Kock: Vrije Universiteit Amsterdam
Brian R. Lee: Allen Institute for Brain Science
Kimberly Smith: Allen Institute for Brain Science
Jonathan T. Ting: Allen Institute for Brain Science
Ed S. Lein: Allen Institute for Brain Science
Huibert D. Mansvelder: Vrije Universiteit Amsterdam
Natalia A. Goriounova: Vrije Universiteit Amsterdam

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract GWAS have identified numerous genes associated with human cognition but their cell type expression profiles in the human brain are unknown. These genes overlap with human accelerated regions (HARs) implicated in human brain evolution and might act on the same biological processes. Here, we investigated whether these gene sets are expressed in adult human cortical neurons, and how their expression relates to neuronal function and structure. We find that these gene sets are preferentially expressed in L3 pyramidal neurons in middle temporal gyrus (MTG). Furthermore, neurons with higher expression had larger total dendritic length (TDL) and faster action potential (AP) kinetics, properties previously linked to intelligence. We identify a subset of genes associated with TDL or AP kinetics with predominantly synaptic functions and high abundance of HARs.

Date: 2023
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DOI: 10.1038/s41467-023-39946-9

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