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Article Dans Une Revue Nature Human Behaviour Année : 2024

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

Shi-Dong Chen
  • Fonction : Auteur
Jia You
Wei Zhang
  • Fonction : Auteur
Bang-Sheng Wu
  • Fonction : Auteur
Yi-Jun Ge
  • Fonction : Auteur
Shi-Tong Xiang
Jing Du
  • Fonction : Auteur
Kevin Kuo
  • Fonction : Auteur
Tobias Banaschewski
Gareth Barker
Arun Bokde
Sylvane Desrivières
Herta Flor
Antoine Grigis
  • Fonction : Auteur
Hugh Garavan
  • Fonction : Auteur
Penny Gowland
Andreas Heinz
Rüdiger Brühl
Frauke Nees
  • Fonction : Auteur
Dimitri Papadopoulos Orfanos
Herve Lemaitre
Tomáš Paus
Luise Poustka
  • Fonction : Auteur
Sarah Hohmann
Sabina Millenet
  • Fonction : Auteur
Christian Baeuchl
  • Fonction : Auteur
Michael Smolka
Nilakshi Vaidya
Henrik Walter
Robert Whelan
  • Fonction : Auteur
Gunter Schumann
Jian-Feng Feng
Qiang Dong
Wei Cheng
Jin-Tai Yu

Résumé

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.
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Dates et versions

hal-04469301 , version 1 (20-02-2024)

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Shi-Dong Chen, Jia You, Wei Zhang, Bang-Sheng Wu, Yi-Jun Ge, et al.. The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders. Nature Human Behaviour, 2024, ⟨10.1038/s41562-023-01792-6⟩. ⟨hal-04469301⟩
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