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. de Witt Hamer; David P. Noske; Christiaan P.J. de Kock; Brian R. Lee; Kimberly Smith; Jonathan T. Ting; Ed S. Lein; Huibert D. Mansvelder; Natalia A. Goriounova

doi:10.1038/s41467-023-39946-9

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. de Witt Hamer
, David P. Noske
, Christiaan P.J. de Kock
, Brian R. Lee
, Kimberly Smith
, Jonathan T. Ting
, Ed S. Lein
, Huibert D. Mansvelder
, Natalia A. Goriounova^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

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.

Original language	English
Article number	4188
Pages (from-to)	1-14
Number of pages	14
Journal	Nature Communications
Volume	14
Early online date	13 Jul 2023
DOIs	https://doi.org/10.1038/s41467-023-39946-9
Publication status	Published - 2023

Bibliographical note

Funding Information:
We thank Prof dr. Danielle Posthuma and dr. Christiaan de Leeuw for their insightful comments on earlier drafts of the manuscript and dr. Sophie van der Sluis for the help with the statistical analyses. This study was supported by several grant awards including award U01MH114812 and UM1MH130981-01 from National Institute of Mental Health (NIMH), grant no. 945539 (Human Brain Project SGA3) from the European Union’s Horizon 2020 Framework Program for Research and Innovation, the Netherlands Organization for Scientific Research (NWO) Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012). N.A.G. is supported by VI.Vidi.213.014 grant from the Netherlands Organization for Scientific Research (NWO). H.D.M. is supported by ERC AdG ‘fasthumanneuron’ 101093198.

Publisher Copyright:
© 2023, The Author(s).

Funding

We thank Prof dr. Danielle Posthuma and dr. Christiaan de Leeuw for their insightful comments on earlier drafts of the manuscript and dr. Sophie van der Sluis for the help with the statistical analyses. This study was supported by several grant awards including award U01MH114812 and UM1MH130981-01 from National Institute of Mental Health (NIMH), grant no. 945539 (Human Brain Project SGA3) from the European Union’s Horizon 2020 Framework Program for Research and Innovation, the Netherlands Organization for Scientific Research (NWO) Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012). N.A.G. is supported by VI.Vidi.213.014 grant from the Netherlands Organization for Scientific Research (NWO). H.D.M. is supported by ERC AdG ‘fasthumanneuron’ 101093198.

Funders	Funder number
European Commission
European Union’s Horizon 2020 Framework Program for Research and Innovation
Nederlandse Organisatie voor Wetenschappelijk Onderzoek	024.004.012
European Research Council	101093198
National Institute of Mental Health	945539

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Driessens, S. L. W., Galakhova, A. A., Heyer, D. B., Pieterse, I. J., Wilbers, R., Mertens, E. J., Waleboer, F., Heistek, T. S., Coenen, L., Meijer, J. R., Idema, S., de Witt Hamer, P. C., Noske, D. P., de Kock, C. P. J., Lee, B. R., Smith, K., Ting, J. T., Lein, E. S., Mansvelder, H. D., & Goriounova, N. A. (2023). Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types. Nature Communications, 14, 1-14. Article 4188. https://doi.org/10.1038/s41467-023-39946-9

@article{b182b4516e574a498a3690864f65a5cb,

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

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.",

author = "Driessens, \{Stan L.W.\} and Galakhova, \{Anna A.\} and Heyer, \{Djai B.\} and Pieterse, \{Isabel J.\} and Ren{\'e} Wilbers and Mertens, \{Eline J.\} and Femke Waleboer and Heistek, \{Tim S.\} and Loet Coenen and Meijer, \{Julia R.\} and Sander Idema and \{de Witt Hamer\}, \{Philip C.\} and Noske, \{David P.\} and \{de Kock\}, \{Christiaan P.J.\} and Lee, \{Brian R.\} and Kimberly Smith and Ting, \{Jonathan T.\} and Lein, \{Ed S.\} and Mansvelder, \{Huibert D.\} and Goriounova, \{Natalia A.\}",

note = "Funding Information: We thank Prof dr. Danielle Posthuma and dr. Christiaan de Leeuw for their insightful comments on earlier drafts of the manuscript and dr. Sophie van der Sluis for the help with the statistical analyses. This study was supported by several grant awards including award U01MH114812 and UM1MH130981-01 from National Institute of Mental Health (NIMH), grant no. 945539 (Human Brain Project SGA3) from the European Union{\textquoteright}s Horizon 2020 Framework Program for Research and Innovation, the Netherlands Organization for Scientific Research (NWO) Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012). N.A.G. is supported by VI.Vidi.213.014 grant from the Netherlands Organization for Scientific Research (NWO). H.D.M. is supported by ERC AdG {\textquoteleft}fasthumanneuron{\textquoteright} 101093198. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

doi = "10.1038/s41467-023-39946-9",

language = "English",

volume = "14",

pages = "1--14",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

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Driessens, SLW , Galakhova, AA, Heyer, DB, Pieterse, IJ, Wilbers, R, Mertens, EJ, Waleboer, F, Heistek, TS, Coenen, L, Meijer, JR, Idema, S, de Witt Hamer, PC, Noske, DP, de Kock, CPJ, Lee, BR, Smith, K, Ting, JT, Lein, ES, Mansvelder, HD & Goriounova, NA 2023, 'Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types', Nature Communications, vol. 14, 4188, pp. 1-14. https://doi.org/10.1038/s41467-023-39946-9

TY - JOUR

T1 - Genes associated with cognitive ability and HAR show overlapping expression patterns in human cortical neuron types

AU - Driessens, Stan L.W.

AU - Galakhova, Anna A.

AU - Heyer, Djai B.

AU - Pieterse, Isabel J.

AU - Wilbers, René

AU - Mertens, Eline J.

AU - Waleboer, Femke

AU - Heistek, Tim S.

AU - Coenen, Loet

AU - Meijer, Julia R.

AU - Idema, Sander

AU - de Witt Hamer, Philip C.

AU - Noske, David P.

AU - de Kock, Christiaan P.J.

AU - Lee, Brian R.

AU - Smith, Kimberly

AU - Ting, Jonathan T.

AU - Lein, Ed S.

AU - Mansvelder, Huibert D.

AU - Goriounova, Natalia A.

N1 - Funding Information: We thank Prof dr. Danielle Posthuma and dr. Christiaan de Leeuw for their insightful comments on earlier drafts of the manuscript and dr. Sophie van der Sluis for the help with the statistical analyses. This study was supported by several grant awards including award U01MH114812 and UM1MH130981-01 from National Institute of Mental Health (NIMH), grant no. 945539 (Human Brain Project SGA3) from the European Union’s Horizon 2020 Framework Program for Research and Innovation, the Netherlands Organization for Scientific Research (NWO) Gravitation program BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (NWO: 024.004.012). N.A.G. is supported by VI.Vidi.213.014 grant from the Netherlands Organization for Scientific Research (NWO). H.D.M. is supported by ERC AdG ‘fasthumanneuron’ 101093198. Publisher Copyright: © 2023, The Author(s).

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

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UR - https://www.scopus.com/pages/publications/85164846362#tab=citedBy

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DO - 10.1038/s41467-023-39946-9

M3 - Article

C2 - 37443107

AN - SCOPUS:85164846362

SN - 2041-1723

VL - 14

SP - 1

EP - 14

JO - Nature Communications

JF - Nature Communications

M1 - 4188

ER -

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

Abstract

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