Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry

作者：Megan Skelton, Brittany L. Mitchell, Elham Assary, Danyang Li, Geneviève Morneau‐Vaillancourt, Alan E Murphy, Abigail R. ter Kuile, Rujia Wang, Mark J. Adams, Enda M. Byrne, Elizabeth C. Corfield, P Grimes, Laurie J. Hannigan, Jihua Hu, Kadri Kõiv, Alex S. F. Kwong, Sergi Papiol, Johanne Hagen Pettersen, Giorgio Pistis, Enrique Castelao, Nora I. Strom, Peter J. van der Most, Silviu‐Alin Bacanu, Rosa Cheesman, Kirstin L. Purves, Hüseyin Gedik, Annika B. Faucon, Kritika Singh, Lucia Colodro-Conde, Kristi Krebs, Per Hoffmann, Stefan Herms, Jan Gehlen, Stephan Ripke, Swapnil Awasthi, Teemu Palviainen, Elisa M. Tasanko, Roseann E. Peterson, Daniel E. Adkins, Andrey A. Shabalin, Matthew H. Iveson, A V Campbell, Laurent F. Thomas, Bendik S. Winsvold, Ole Kristian Drange, Sigrid Børte, Abigail R. ter Kuile, Tan-Hoang Nguyen, Sandra M. Meier, Daniel F. Levey, D Czamara, Karmel W. Choi, Baptiste Couvy-Duchesne, Sandra van der Auwera, Alexander Teumer, Robert Karlsson, Miguel Garcia-Argibay, Donghyung Lee, Ottar Bjerkeset, Eystein Stordal, Julia Bäckmann, Giovanni A. Salum, Clement Zai, James L. Kennedy, Gwyneth Zai, Arun K. Tiwari, Stefanie Heilmann-Heimbach, Börge Schmidt, Jaakko Kaprio, Martin M. Kennedy, Joseph Boden, Christel M. Middeldorp, Fabiana L. Lopes, Nirmala Akula, Francis J. McMahon, E Binder, Lydia Fehm, Andreas Ströhle, Henning Tiemeier, Dan J. Stein, David Whiteman, Catherine Olsen, Zachary Fuller, Xin Wang, Glyn Lewis, Nicholas J. Timpson, Lea K. Davis, Nathan A. Gillespie, Lili Milani, Johannes Schumacher, David P. Woldbye, Andreas J. Forstner, Markus M. Nöthen, Iiris Hovatta, John Horwood, Hermine H. Maes, John-Anker Zwart, Ole Mors, Anders D. Børglum, Preben B. Mortensen, Helga Ask, Ted Reichborn‐Kjennerud, Jackob M. Najman, M T Stein, Joel Gelernter, Yuri Milaneschi, Brenda W. Penninx, Dorret I. Boomsma, Eduard Maron, Christian Rück, Tilo T. Kircher, Christiane A. Melzig, Georg W. Alpers, Volker Arolt, Jordan W. Smoller, A Luik, H J Grabe, Henrik Larsson, Patrik K. Magnusson, Anna R. Docherty, Hilary Coon, Rupert Conrad, Manuel Mattheisen, GLAD+ authors, Matthew Hotopf, I Jones, D N Smith, Allan H. Young, Antony J. Cleare, Katrina A. S. Davis, Georgina Krebs, Katharine A. Rimes, David Veale, Roland Zahn, Molly R. Davies, Gursharan Kalsi, Shannon Bristow, Susannah C.B. Curzons, Henry C. Rogers, Katherine N. Thompson, Brett N. Adey, Ian Marsh, Dina Monssen, Monika McAtarsney‐Kovacs, Charles J. Curtis, Jahnavi Arora, Saakshi Kakar, Laura Meldrum, Iona Smith, Le Roy Dowey, Victor Gault, Donald M. Lyall, Ruth K. Price, Keith Thomas, Zain Ahmad, Helena L. Davies, Christopher Hübel, Sang Hyuck Lee, Yuhao “Leo” Lin, Jared G. Maina, Jessica Mundy, Alish Palmos, Alicia J. Peel, Christopher Rayner, Johan Zvrskovec, Lifelines Cohort Study, Raul Aguirre-Gamboa, Patrick Deelen, Lude Franke, Jan A. Kuivenhoven, Esteban A. Lopera-Maya, Ilja M. Nolte, Serena Sanna, Morris A. Swertz, Peter M. Visscher, J M Vonk, Cisca Wijmenga, NIHR BioResource, John Bradley, Nathalie Kingston, Hannah Stark, Carola Kanz, Alexei Moulton, Nigel Ovington, Jacinta Lee, Debbie Clapham-Riley, Katie Mills, U. Wittchen, Andre Pittig, Ingmar Heinig, Jürgen Hoyer, Thomas Fydrich, Alfons Hamm, Jan Richter, Volker Arolt, Katja Kölkebeck, Sylvia Schneider, J Margraf, Benjamin Straube, Winfried Rief, Paul Pauli, Peter Neudeck, Ole A. Andreassen, Angelika Erhardt-Lehmann, Alexandra Havdahl, Nathan Skene, Brad Verhulst, Heike Weber, Chérie Armour, Helga Ask, William Copeland, Udo Dannlowski, Jürgen Deckert, Katharina Domschke, Ian B. Hickie, Kelli Lehto, Tina B. Lonsdorf, Ulrike Lueken, Michelle K. Lupton, Sarah E. Medland, Andrew M. McIntosh, Albertine J. Oldehinkel, Martin Preisig, Andreas Reif, Harold Snieder, James Walters, Naomi R. Wray, Catharina A. Hartman, Nicholas G. Martin, John M. Hettema, Gerome Breen, Jonathan R. I. Coleman, T. C. Eley · 发表于：Nature Human Behaviour · 年份：2026 · DOI：10.1038/s41562-026-02476-7 · 被引用次数：1 · 研究领域：Genetic Associations and Epidemiology、Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes、Neurotransmitter Receptor Influence on Behavior

Abstract Anxiety is heritable and exists on a continuum, with symptoms ranging from adaptive threat response to clinical disorder. Here we performed a genome-wide association meta-analysis of generalized anxiety symptom severity in 693,869 individuals of European ancestry from 14 cohorts. We identified 80 independent genome-wide significant variants within 74 loci, 39 of which were newly associated with anxiety. SNP-based heritability was 5.9% (posterior s.d. = 0.15%). Polygenic scores were significantly associated with anxiety symptom severity and disorder in European, African and South Asian ancestry samples ( R 2 = 1.2–2.9%). Significant genetic correlations ( r g ) were estimated with mental and physical health traits, including case–control anxiety, neuroticism and depression ( r g = 0.71–0.85), irritable bowel syndrome ( r g = 0.57), coronary artery disease, endometriosis and migraine ( r g = 0.20–0.27). Gene-based and pathway analyses implicated synaptic and axonal processes, with enriched expression in the brain. These findings highlight the discovery power gained from analysing a quantitative trait rather than a case–control phenotype in anxiety genetics.