| Title: |
Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling |
| Authors: |
Strom, Nora I.; Verhulst, Brad; Bacanu, Silviu-Alin; Cheesman, Rosa; Purves, Kirstin L.; Gedik, Hüseyin; Mitchell, Brittany L.; Kwong, Alex S.; Faucon, Annika B.; Singh, Kritika; Medland, Sarah; 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.; Adams, Mark J.; 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.; Corfield, Elizabeth C.; Hannigan, Laurie; Levey, Daniel F.; Czamara, Darina; Weber, Heike; Choi, Karmel W.; Pistis, Giorgio; Couvy-Duchesne, Baptiste; Van der Auwera, Sandra; Teumer, Alexander; Karlsson, Robert; Garcia-Argibay, Miguel; Lee, Donghyung; Wang, Rujia; 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; Havdahl, Alexandra; Middeldorp, Christel M.; Lopes, Fabiana L.; Akula, Nirmala; McMahon, Francis J.; Binder, Elisabeth B.; Fehm, Lydia; Ströhle, Andreas; Castelao, Enrique; Tiemeier, Henning; Stein, Dan J.; Whiteman, David; Olsen, Catherine; Fuller, Zachary; Wang, Xin; Wray, Naomi R.; Byrne, Enda M.; Lewis, Glyn; Timpson, Nicholas J.; Davis, Lea K.; Hickie, Ian B.; Gillespie, Nathan A.; Milani, Lili; Schumacher, Johannes; Woldbye, David P.; Forstner, Andreas J.; Nöthen, Markus M.; Hovatta, Iiris; Horwood, John; Copeland, William E.; Maes, Hermine H.; McIntosh, Andrew M.; Andreassen, Ole A.; 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; Erhardt-Lehmann, Angelika; Rück, Christian; Kircher, Tilo T.; Melzig, Christiane A.; Alpers, Georg W.; Arolt, Volker; Domschke, Katharina; Smoller, Jordan W.; Preisig, Martin; Martin, Nicholas G.; Lupton, Michelle K.; Luik, Annemarie I.; Reif, Andreas; Grabe, Hans J.; Larsson, Henrik; Magnusson, Patrik K.; Oldehinkel, Albertine J.; Hartman, Catharina A.; Breen, Gerome; Docherty, Anna R.; Coon, Hilary; Conrad, Rupert; Lehto, Kelli; 23andMe; the Million Veteran Program; FinnGen; Deckert, Jürgen; Eley, Thalia C.; Mattheisen, Manuel; Hettema, John M. |
| Contributors: |
Institute for Molecular Medicine Finland; Genetic Epidemiology; Helsinki Institute of Life Science HiLIFE; Mind and Matter; Department of Psychology; Iiris Hovatta / Principal Investigator; Medicum; SLEEPWELL Research Program; Faculty of Medicine |
| Publisher Information: |
Nature Research |
| Publication Year: |
2026 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Biomedicine |
| Description: |
The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder, and phobias) are highly prevalent, often onset early, persist throughout life, and cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant ANX risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 of the 58 associated variants were replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism, and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism underlying ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.Competing Interest StatementPer Hoffmann receives Salary from the Life amp; Brain GmbH, Bonn, Germany. James L. Kennedy is a member of the Scientific Advisory Board for Myriad Neuroscience Inc. Ian B. Hickie was an inaugural Commissioner on Australia’s National Mental Health Commission (2012-18). He is the Co-Director, Health and Policy at the Brain and Mind Centre (BMC) University of Sydney. The BMC operates an early-intervention youth services at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 5 InnoWell Pty Ltd. InnoWell was formed by the University of Sydney (45 and PwC (Australia; 45 to deliver the $30 M Australian Government-funded Project Synergy (2017-20; a three-year program for the transformation of mental health services) and to lead transformation of mental health services internationally through the use of innovative ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
Bibtex: Strom2024.07.03.24309466; https://hdl.handle.net/10138/628213 |
| Availability: |
https://hdl.handle.net/10138/628213 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.805381AA |
| Database: |
BASE |