Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry
Year: 2026
Type: review
Study design: Observational Study
Abstract: Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestryAnxiety 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 casecontrol 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.
Source: MPG.PuRe (Max Planck Society)
Authors: Skelton, Megan, Mitchell, Brittany L., Assary, Elham, Li, Danyang, Morneau-Vaillancourt, Genevieve, Murphy, Alan E., ter Kuile, Abigail R., Wang, Rujia, Adams, Mark J., Byrne, Enda M., Corfield, Elizabeth C., Grimes, Poppy Z., Hannigan, Laurie J., Hu, Jihua, Kõiv, Kadri, Kwong, Alex S. F., Papiol, Sergi, Pettersen, Johanne H., Pistis, Giorgio, Castelao, Enrique, Strom, Nora I., van der Most, Peter J., Bacanu, Silviu-Alin, Cheesman, Rosa, Purves, Kirstin L., Gedik, Hüseyin, Faucon, Annika B., Singh, Kritika, Colodro-Conde, Lucia, Krebs, Kristi, Hoffmann, Per, Herms, Stefan, Gehlen, Jan, Ripke, Stephan, Awasthi, Swapnil, Palviainen, Teemu, Tasanko, Elisa M., Peterson, Roseann E., Adkins, Daniel E., Shabalin, Andrey A., Iveson, Matthew H., Campbell, Archie, Thomas, Laurent F., Winsvold, Bendik S., Drange, Ole Kristian, Børte, Sigrid, ter Kuile, Abigail R., Nguyen, Tan-Hoang, Meier, Sandra M., Levey, Daniel F., Czamara, Darina, Choi, Karmel W., Couvy-Duchesne, Baptiste, Van der Auwera, Sandra, Teumer, Alexander, Karlsson, Robert, Garcia-Argibay, Miguel, Lee, Donghyung, Bjerkeset, Ottar, Stordal, Eystein, Bäckmann, Julia, Salum, Giovanni A., Zai, Clement C., Kennedy, James L., Zai, Gwyneth, Tiwari, Arun K., Heilmann-Heimbach, Stefanie, Schmidt, Börge, Kaprio, Jaakko, Kennedy, Martin M., Boden, Joseph, Middeldorp, Christel M., Lopes, Fabiana L., Akula, Nirmala, McMahon, Francis J., Binder, Elisabeth B., Fehm, Lydia, Ströhle, Andreas, Tiemeier, Henning, Stein, Dan J., Whiteman, David, Olsen, Catherine, Fuller, Zachary, Wang, Xin, Lewis, Glyn, Timpson, Nicholas J., Davis, Lea K., Gillespie, Nathan A., Milani, Lili, Schumacher, Johannes, Woldbye, David P., Forstner, Andreas J., Nöthen, Markus M., Hovatta, Iiris, Horwood, John, Maes, Hermine H., Zwart, John-Anker, Mors, Ole, Børglum, Anders D., Mortensen, Preben B., Ask, Helga, Reichborn-Kjennerud, Ted, Najman, Jackob M., Stein, Murray B., Gelernter, Joel, Milaneschi, Yuri, Penninx, Brenda W., Boomsma, Dorret I., Maron, Eduard, Rück, Christian, Kircher, Tilo T., Melzig, Christiane A., Alpers, Georg W., Arolt, Volker, Smoller, Jordan W., Luik, Annemarie I., Grabe, Hans J., Larsson, Henrik, Magnusson, Patrik K., Docherty, Anna R., Coon, Hilary, Conrad, Rupert, Mattheisen, Manuel, Hotopf, Matthew, Jones, Ian R., Smith, Daniel J., Young, Allan H., Cleare, Antony J., Davis, Katrina A. S., Krebs, Georgina, Rimes, Katharine A., Veale, David, Zahn, Roland, Davies, Molly R., Kalsi, Gursharan, Bristow, Shannon, Curzons, Susannah C. B., Rogers, Henry C., Thompson, Katherine N., Adey, Brett N., Marsh, Ian, Monssen, Dina, McAtarsney-Kovacs, Monika, Curtis, Charles J., Arora, Jahnavi, Kakar, Saakshi, Meldrum, Laura, Smith, Iona, Dowey, Le Roy, Gault, Victor, Lyall, Donald M., Price, Ruth K., Thomas, Keith G., Ahmad, Zain, Davies, Helena L., Hübel, Christopher, Lee, Sang Hyuck, Lin, Yuhao “Leo”, Maina, Jared G., Mundy, Jessica, Palmos, Alish, Peel, Alicia J., Rayner, Christopher, Zvrskovec, Johan, Aguirre-Gamboa, Raul, Deelen, Patrick, Franke, Lude, Kuivenhoven, Jan A., Lopera Maya, Esteban A., Nolte, Ilja M., Sanna, Serena, Swertz, Morris A., Visscher, Peter M., Vonk, Judith M., Wijmenga, Cisca, Bradley, John, Kingston, Nathalie, Stark, Hannah, Kanz, Carola, Moulton, Alexei, Ovington, Nigel, Lee, Jacinta, Clapham-Riley, Debbie, Mills, Katie, Wittchen, Uli, Pittig, Andre, Heinig, Ingmar, Hoyer, Jürgen, Fydrich, Thomas, Hamm, Alfons, Richter, Jan, Arolt, Volker, Kölkebeck, Katja, Schneider, Sylvia, Margraf, Jürgen, Straube, Benjamin, Rief, Winfried, Pauli, Paul, Neudeck, Peter, Andreassen, Ole A., Erhardt-Lehmann, Angelika, Havdahl, Alexandra, Skene, Nathan, Verhulst, Brad, Weber, Heike, Armour, Chérie, Ask, Helga, Copeland, William E., Dannlowski, Udo, Deckert, Jürgen, Domschke, Katharina, Hickie, Ian B., Lehto, Kelli, Lonsdorf, Tina B., Lueken, Ulrike, Lupton, Michelle K., Medland, Sarah E., McIntosh, Andrew M., Oldehinkel, Albertine J., Preisig, Martin, Reif, Andreas, Snieder, Harold, Walters, James T. R., Wray, Naomi R., Hartman, Catharina A., Martin, Nicholas G., Hettema, John M., Breen, Gerome, Coleman, Jonathan R. I., Eley, Thalia C.
Institution: Forschungszentrum Jülich
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: National Science Foundation, GlaxoSmithKline, Office of Research and Development, NHS Blood and Transplant, Queensland Health, Wellcome Trust, Scottish Government, Maudsley Charity, UK Research and Innovation, Trond Mohn stiftelse, Jan Dekker Stichting, National Institute for Health and Care Research, Department of Health and Social Care, Scottish Funding Council, King's College London, European Commission, European Science Foundation, University of Bristol, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Rijksuniversiteit Groningen, ZonMw, Eesti Teadusagentuur, Bundesministerium für Bildung und Forschung, Ministerie van Volksgezondheid, Welzijn en Sport, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Accare, Novo Nordisk, NordForsk, Universitetet i Bergen, Universitair Medisch Centrum Groningen, Universitetet i Oslo, Norges Forskningsråd, Wetenschappelijk Onderzoek- en Documentatiecentrum, Tartu Ülikool, Novo Nordisk Fonden, UK Dementia Research Institute, South East Regional Health Authority, National Institutes of Health, Chief Scientist Office, Scottish Government Health and Social Care Directorate, NIHR BioResource, Medical Research Council, National Health and Medical Research Council, Helse Sør-Øst RHF, Norwegian Institute of Public Health, National Institute of Mental Health
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