Nora I. Strom, Brad Verhulst, Silviu-Alin Bacanu, Rosa Cheesman, Kirstin L. Purves, Hüseyin Gedik, Brittany L. Mitchell, Alex S F Kwong, Annika Faucon, Kritika Singh, Sarah Medland, 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, Adams Mark J., Matthew H. Iveson, Archie Campbell, Laurent F. Thomas, Bendik S. Winsvold, Ole Kristian Drange, Sigrid Børte, Abigail ter Kuile, Joonas Naamanka, Tan-Hoang Nguyen, Sandra M. Meier, Elizabeth C. Corfield, Laurie J. Hannigan, Daniel F. Levey, Darina Czamara, Heike Weber, Karmel W. Choi, Giorgio Pistis, Baptiste Couvy-Duchesne, Sandra Van der Auwera, Alexander Teumer, Robert Karlsson, Miguel Garcia-Argibay, Donghyung Lee, Rujia Wang, Ottar Bjerkeset, Eystein Stordal, Julia Bäckman, 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, Alexandra Havdahl, Christel M. Middeldorp, Fabiana L. Lopes, Nirmala Akula, Francis J. McMahon, Elisabeth B. Binder, Lydia Fehm, Andreas Ströhle, Enrique Castelao, Henning Tiemeier, Dan J. Stein, David C Whiteman, Catherine Olsen, Zachary L. Fuller, Xin Eric Wang, Naomi R. Wray, Enda M. Byrne, Glyn Lewis, Nicholas J. Timpson, Lea K. Davis, Ian B. Hickie, Nathan A. Gillespie, Lili Milani, Johannes Schumacher, David P.D. Woldbye, Andreas J. Forstner, Markus M. Nöthen, Iiris Hovatta, John Horwood, William E. Copeland, Hermine H. Maes, Andrew M. McIntosh, Ole A. Andreassen, John-Anker Zwart, Ole Mors, Anders D. Børglum, Preben B. Mortensen, Helga Ask, Ted Reichborn-Kjennerud
The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder and phobias) are highly prevalent, often onset early and cause substantial global disability. Although distinct in their clinical presentations, they probably 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 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 out of the 58 associations 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 implicated in ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.