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The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders.
Chen, Shi-Dong; You, Jia; Zhang, Wei; Wu, Bang-Sheng; Ge, Yi-Jun; Xiang, Shi-Tong; Du, Jing; Kuo, Kevin; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Desrivières, Sylvane; Flor, Herta; Grigis, Antoine; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Brühl, Rüdiger; Martinot, Jean-Luc; Martinot, Marie-Laure Paillère; Artiges, Eric; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Lemaitre, Herve; Paus, Tomás; Poustka, Luise; Hohmann, Sarah; Millenet, Sabina; Baeuchl, Christian; Smolka, Michael N; Vaidya, Nilakshi; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Feng, Jian-Feng; Dong, Qiang; Cheng, Wei; Yu, Jin-Tai.
Afiliação
  • Chen SD; Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
  • You J; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
  • Zhang W; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
  • Wu BS; Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
  • Ge YJ; Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
  • Xiang ST; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
  • Du J; Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
  • Kuo K; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
  • Banaschewski T; Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
  • Barker GJ; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Bokde ALW; Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
  • Desrivières S; Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
  • Flor H; Institute of Psychiatry, Psychology & Neuroscience, Social, Genetic, Developmental Psychiatry Centre, King's College London, London, UK.
  • Grigis A; Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Garavan H; Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany.
  • Gowland P; NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
  • Heinz A; Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA.
  • Brühl R; Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, Nottingham, UK.
  • Martinot JL; Department of Psychiatry and Psychotherapy CCM, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Martinot MP; Physikalisch-Technische Bundesanstalt (PTB), Braunschweig and Berlin, Germany.
  • Artiges E; Institut National de la Santé et de la Recherche Médicale, INSERM U 1299 "Trajectoires développementales & psychiatrie", University Paris-Saclay, CNRS, Ecole Normale Supérieure Paris-Saclay, Centre Borelli, Gif-sur-Yvette, France.
  • Nees F; Institut National de la Santé et de la Recherche Médicale, INSERM U 1299 "Trajectoires développementales & psychiatrie", University Paris-Saclay, CNRS, Ecole Normale Supérieure Paris-Saclay, Centre Borelli, Gif-sur-Yvette, France.
  • Orfanos DP; AP-HP, Sorbonne University, Department of Child and Adolescent Psychiatry, Pitié-Salpêtrière Hospital, Paris, France.
  • Lemaitre H; Institut National de la Santé et de la Recherche Médicale, INSERM U 1299 "Trajectoires développementales & psychiatrie", University Paris-Saclay, CNRS, Ecole Normale Supérieure Paris-Saclay, Centre Borelli, Gif-sur-Yvette, France.
  • Paus T; Psychiatry Department, EPS Barthélémy Durand, Etampes, France.
  • Poustka L; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Hohmann S; Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Millenet S; Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany.
  • Baeuchl C; NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
  • Smolka MN; NeuroSpin, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
  • Vaidya N; Institut des Maladies Neurodégénératives, UMR 5293, CNRS, CEA, Université de Bordeaux, Bordeaux, France.
  • Walter H; Departments of Psychiatry and Neuroscience, Faculty of Medicine and Centre Hosptalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada.
  • Whelan R; Departments of Psychiatry and Psychology, University of Toronto, Toronto, Ontario, Canada.
  • Schumann G; Department of Child and Adolescent Psychiatry and Psychotherapy, University Medical Centre Göttingen, Göttingen, Germany.
  • Feng JF; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Dong Q; Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
  • Cheng W; Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
  • Yu JT; Centre for Population Neuroscience and Stratified Medicine (PONS), Department of Psychiatry and Neuroscience, Charité Universitätsmedizin Berlin, Berlin, Germany.
Nat Hum Behav ; 8(4): 779-793, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38182882
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estudo de Associação Genômica Ampla / Hipotálamo Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estudo de Associação Genômica Ampla / Hipotálamo Idioma: En Ano de publicação: 2024 Tipo de documento: Article