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 - 2023/7/13
Y1 - 2023/7/13
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.ncbi.nlm.nih.gov/pubmed/37443107
U2 - https://doi.org/10.1038/s41467-023-39946-9
DO - https://doi.org/10.1038/s41467-023-39946-9
M3 - Article
C2 - 37443107
SN - 2041-1723
VL - 14
SP - 1
EP - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4188
ER -