Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study.

Autor: Friligkou E; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA., Løkhammer S; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Clinical Science, University of Bergen, Bergen, Norway.; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway., Cabrera-Mendoza B; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA., Shen J; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China., He J; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA., Deiana G; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Center for Neuroscience, Pharmacology Unit, School of Pharmacy, University of Camerino, Camerino, Italy., Zanoaga MD; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland., Asgel Z; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Department of Child and Adolescent Psychiatry, NYU Langone Health, New York Metropolitan Area, New York, NY, USA., Pilcher A; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA., Di Lascio L; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy; Humanitas University, Pieve Emanuele, Milan, Italy., Makharashvili A; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; 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.; Department of Genetics, Microbiology and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Spain., Tylee DS; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA., Pathak GA; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.; Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA., Polimanti R; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA. renato.polimanti@yale.edu.; Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT, USA. renato.polimanti@yale.edu.; Wu Tsai Institute, Yale University, New Haven, CT, USA. renato.polimanti@yale.edu.; Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA. renato.polimanti@yale.edu.; Department of Biomedical Informatics and Data Science, Yale School of Medicine, New Haven, CT, USA. renato.polimanti@yale.edu.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2024 Oct; Vol. 56 (10), pp. 2036-2045. Date of Electronic Publication: 2024 Sep 18.
DOI: 10.1038/s41588-024-01908-2
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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