The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders

Shi-Dong Chen, Jia You, Wei Zhang, Bang-Sheng Wu, Yi-Jun Ge, Shi-Tong Xiang, Jing Du, Kevin Kuo, Tobias Banaschewski, Gareth J. Barker, Arun L. W. Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Herve Lemaitre, Tomáš Paus, Luise Poustka, Sarah Hohmann, Sabina Millenet, Christian Baeuchl, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Jian-Feng Feng (), Qiang Dong (), Wei Cheng () and Jin-Tai Yu ()
Additional contact information
Shi-Dong Chen: Fudan University, National Center for Neurological Disorders
Jia You: Fudan University
Wei Zhang: Fudan University
Bang-Sheng Wu: Fudan University, National Center for Neurological Disorders
Yi-Jun Ge: Fudan University, National Center for Neurological Disorders
Shi-Tong Xiang: Fudan University
Jing Du: Fudan University, National Center for Neurological Disorders
Kevin Kuo: Fudan University, National Center for Neurological Disorders
Tobias Banaschewski: Heidelberg University
Gareth J. Barker: King’s College London
Arun L. W. Bokde: Trinity College Dublin
Sylvane Desrivières: King’s College London
Herta Flor: Heidelberg University
Antoine Grigis: Université Paris-Saclay
Hugh Garavan: University of Vermont
Penny Gowland: University of Nottingham
Andreas Heinz: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Rüdiger Brühl: Physikalisch-Technische Bundesanstalt (PTB)
Jean-Luc Martinot: Centre Borelli
Marie-Laure Paillère Martinot: Centre Borelli
Eric Artiges: Centre Borelli
Frauke Nees: Heidelberg University
Dimitri Papadopoulos Orfanos: Université Paris-Saclay
Herve Lemaitre: Université Paris-Saclay
Tomáš Paus: University of Montreal
Luise Poustka: University Medical Centre Göttingen
Sarah Hohmann: University Medical Center Hamburg-Eppendorf
Sabina Millenet: Heidelberg University
Christian Baeuchl: Technische Universität Dresden
Michael N. Smolka: Technische Universität Dresden
Nilakshi Vaidya: Charité Universitätsmedizin Berlin
Henrik Walter: Humboldt-Universität zu Berlin, and Berlin Institute of Health
Robert Whelan: Trinity College Dublin
Gunter Schumann: Charité Universitätsmedizin Berlin
Jian-Feng Feng: Fudan University
Qiang Dong: Fudan University, National Center for Neurological Disorders
Wei Cheng: Fudan University, National Center for Neurological Disorders
Jin-Tai Yu: Fudan University, National Center for Neurological Disorders

Nature Human Behaviour, 2024, vol. 8, issue 4, 779-793

Abstract: Abstract Despite its crucial role in the regulation of vital metabolic and neurological functions, the genetic architecture of the hypothalamus remains unknown. Here we conducted multivariate genome-wide association studies (GWAS) using hypothalamic imaging data from 32,956 individuals to uncover the genetic underpinnings of the hypothalamus and its involvement in neuropsychiatric traits. There were 23 significant loci associated with the whole hypothalamus and its subunits, with functional enrichment for genes involved in intracellular trafficking systems and metabolic processes of steroid-related compounds. The hypothalamus exhibited substantial genetic associations with limbic system structures and neuropsychiatric traits including chronotype, risky behaviour, cognition, satiety and sympathetic–parasympathetic activity. The strongest signal in the primary GWAS, the ADAMTS8 locus, was replicated in three independent datasets (N = 1,685–4,321) and was strengthened after meta-analysis. Exome-wide association analyses added evidence to the association for ADAMTS8, and Mendelian randomization showed lower ADAMTS8 expression with larger hypothalamic volumes. The current study advances our understanding of complex structure–function relationships of the hypothalamus and provides insights into the molecular mechanisms that underlie hypothalamic formation.

Date: 2024
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41562-023-01792-6 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nathum:v:8:y:2024:i:4:d:10.1038_s41562-023-01792-6

Ordering information: This journal article can be ordered from
https://www.nature.com/nathumbehav/

DOI: 10.1038/s41562-023-01792-6

Access Statistics for this article

Nature Human Behaviour is currently edited by Stavroula Kousta

More articles in Nature Human Behaviour from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().