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Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study.
Friligkou, Eleni; Løkhammer, Solveig; Cabrera-Mendoza, Brenda; Shen, Jie; He, Jun; Deiana, Giovanni; Zanoaga, Mihaela Diana; Asgel, Zeynep; Pilcher, Abigail; Di Lascio, Luciana; Makharashvili, Ana; Koller, Dora; Tylee, Daniel S; Pathak, Gita A; Polimanti, Renato.
Afiliación
  • Friligkou E; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
  • Løkhammer S; Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA.
  • Cabrera-Mendoza B; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
  • Shen J; Department of Clinical Science, University of Bergen, Bergen, Norway.
  • He J; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
  • Deiana G; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
  • Zanoaga MD; Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA.
  • Asgel Z; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
  • Pilcher A; Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China.
  • Di Lascio L; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
  • Makharashvili A; Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA.
  • Koller D; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
  • Tylee DS; Center for Neuroscience, Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy.
  • Pathak GA; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
  • Polimanti R; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Nat Genet ; 2024 Sep 18.
Article en En | MEDLINE | ID: mdl-39294497
ABSTRACT
We leveraged information from more than 1.2 million participants, including 97,383 cases, to investigate the genetics of anxiety disorders across five continental groups. Through ancestry-specific and cross-ancestry genome-wide association studies, we identified 51 anxiety-associated loci, 39 of which were novel. In addition, polygenic risk scores derived from individuals of European descent were associated with anxiety in African, admixed American and East Asian groups. The heritability of anxiety was enriched for genes expressed in the limbic system, cerebral cortex, cerebellum, metencephalon, entorhinal cortex and brain stem. Transcriptome-wide and proteome-wide analyses highlighted 115 genes associated with anxiety through brain-specific and cross-tissue regulation. Anxiety also showed global and local genetic correlations with depression, schizophrenia and bipolar disorder and widespread pleiotropy with several physical health domains. Overall, this study expands our knowledge regarding the genetic risk and pathogenesis of anxiety disorders, highlighting the importance of investigating diverse populations and integrating multi-omics information.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos