Published: 15-01-2025 08:10 | Updated: 15-01-2025 08:35

Global study pinpoints genes for depression across ethnicities

Genre picture of a DNA helix.
DNA helix. Photo: Gettyimages

New genetic risk factors for depression have been identified across all major global populations for the first time, allowing scientists to predict risk of depression regardless of ethnicity. The world’s largest and most diverse genetic study ever of major depression has revealed nearly 300 previously unknown genetic links to the condition.

Lu Yi
Lu Yi, principal researcher at the Department of Medical Epidemiology and Biostatistics. Photo: Ulf Sirborn

The research has uncovered nearly 300 new genetic factors linked to depression, making it the most diverse and comprehensive genetic study ever conducted on this condition. These findings are significant because they include individuals from a wide variety of ethnic backgrounds—such as African, East Asian, Hispanic, and South Asian populations—helping to identify genetic factors relevant to people across the globe, not just those of European descent. This research also shows that these genetic variants are associated with brain cells that control emotions, offering new insights into how depression affects the brain.

Potential for more effective treatment for depression

These results are crucial because they provide a more inclusive understanding of depression’s genetic basis, addressing a major gap in previous studies that mostly focused on people of European ancestry. By including diverse populations, we can now more accurately predict an individual’s risk for depression, regardless of their ethnicity. This has the potential to lead to more effective, personalized treatments for depression, reducing the existing health inequalities caused by previous research biases. Furthermore, our study identifies new targets for potential treatments, which could lead to more effective therapies for people worldwide.

Genetic data from over 5 million people

The research team from the Psychiatric Genomics Consortium involved scientists from all continents, including studies from South Africa, Brazil, Mexico, the USA, Australia, Taiwan and China which together analyzed genetic data from over 5 million people across 29 countries. The dataset was diverse, with one in four participants coming from non-European ancestries. The focus was on small differences in DNA that can influence a person’s susceptibility to depression. The results revealed nearly 700 genetic factors linked to depression, with almost half of them being previously unknown. Now over 300 genes are implicated as involved in the development of depression.

Image of Professor Patrick Sullivan
Professor Patrick Sullivan at Karolinska Institutet and University of North Carolina at Chapel Hill.

Future clinical trials

The next step in our research is to further explore the potential of repurposing existing medications for treating depression. For instance, our findings suggest two drugs—pregabalin (used for chronic pain) and modafinil (used for narcolepsy)—that could be effective in treating depression based on our findings. However, before these drugs can be widely used for depression, more clinical trials are necessary to test their safety and efficacy in treating depression specifically. Additionally, the group will continue to study how these genetic variants affect brain function to better understand the biology of depression and develop new, more targeted treatments.

"We are very pleased that more than 5,000 individuals from Sweden with specialist-diagnosed major depression have uniquely contributed to this global effort”, says Lu Yi, Principal Researcher and responsible for the Swedish part of the study. She continues; “This truly represent a major advancement in understanding the biology behind the mental illness that affects so many”. 

Working together in an international team of scientists, in this case led by researchers at the University of Edinburgh and King’s College London, strengthens the possibilities to move forward in this important research field. The team at Karolinska Institutet further consisted of Shuyang Yao, Ying Xiong, Arvid Harder, Patrik Magnusson, Mikael Landén, Patrick Sullivan at the Department of Medical Epidemiology and Biostatistics, Jens Hjerling-Leffler at the Department of Medical Biochemistry and Biophysics and Christian Rück at the Department of Clinical Neuroscience.

The international research team, including researchers at Karolinska Institutet have published their findings in Cell

This news article is based on a press release from the Psychiatric Genomics Consortium. 

Publication

Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies,

Mark J. Adams, Fabian Streit, Xiangrui Meng, Swapnil Awasthi, Brett N. Adey, Karmel W. Choi, V. Kartik Chundru, Jonathan R.I. Coleman, Bart Ferwerda, Jerome C. Foo, Zachary F. Gerring, Olga Giannakopoulou, Priya Gupta, Alisha S.M. Hall, Arvid Harder, David M. Howard, Christopher Hübel, Alex S.F. Kwong, Daniel F. Levey, Brittany L. Mitchell, Guiyan Ni, Vanessa K. Ota, Oliver Pain, Gita A. Pathak, Eva C. Schulte, Xueyi Shen, Jackson G. Thorp, Alicia Walker, Shuyang Yao, Jian Zeng, Johan Zvrskovec, Dag Aarsland, Ky'Era V. Actkins, Mazda Adli, Esben Agerbo, Mareike Aichholzer, Allison Aiello, Tracy M. Air, Thomas D. Als, Evelyn Andersson, Till F.M. Andlauer, Volker Arolt, Helga Ask, Julia Bäckman, Sunita Badola, Clive Ballard, Karina Banasik, Nicholas J. Bass, Aartjan T.F. Beekman, Sintia Belangero, Tim B. Bigdeli, Elisabeth B. Binder, Ottar Bjerkeset, Gyda Bjornsdottir, Sigrid Børte, Emma Bränn, Alice Braun, Thorsten Brodersen, Tanja M. Brückl, Søren Brunak, Mie T. Bruun, Margit Burmeister, Pichit Buspavanich, Jonas Bybjerg-Grauholm, Enda M. Byrne, Jianwen Cai, Archie Campbell, Megan L. Campbell, Adrian I. Campos, Enrique Castelao, Jorge Cervilla, Boris Chaumette, Chia-Yen Chen, Hsi-Chung Chen, Zhengming Chen, Sven Cichon, Lucía Colodro-Conde, Anne Corbett, Elizabeth C. Corfield, Baptiste Couvy-Duchesne, Nick Craddock, Udo Dannlowski, Gail Davies, E.J.C. de Geus, Ian J. Deary, Franziska Degenhardt, Abbas Dehghan, J. Raymond DePaulo, Michael Deuschle, Maria Didriksen, Khoa Manh Dinh, Nese Direk, Srdjan Djurovic, Anna R. Docherty, Katharina Domschke, Joseph Dowsett, Ole Kristian Drange, Erin C. Dunn, William Eaton, Gudmundur Einarsson, Thalia C. Eley, Samar S.M. Elsheikh, Jan Engelmann, Michael E. Benros, Christian Erikstrup, Valentina Escott-Price, Chiara Fabbri, Yu Fang, Sarah Finer, Josef Frank, Robert C. Free, Linda Gallo, He Gao, Michael Gill, Maria Gilles, Fernando S. Goes, Scott Douglas Gordon, Jakob Grove, Daniel F. Gudbjartsson, Blanca Gutierrez, Tim Hahn, Lynsey S. Hall, Thomas F. Hansen, Magnus Haraldsson, Catharina A. Hartman, Alexandra Havdahl, Caroline Hayward, Stefanie Heilmann-Heimbach, Stefan Herms, Ian B. Hickie, Henrik Hjalgrim, Jens Hjerling-Leffler, Per Hoffmann, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Hougaard, Iiris Hovatta, Qin Qin Huang, Donald Hucks, Floris Huider, Karen A. Hunt, Nicholas S. Ialongo, Marcus Ising, Erkki Isometsä, Rick Jansen, Yunxuan Jiang, Ian Jones, Lisa A. Jones, Lina Jonsson, Masahiro Kanai, Robert Karlsson, Siegfried Kasper, Kenneth S. Kendler, Ronald C. Kessler, Stefan Kloiber, James A. Knowles, Nastassja Koen, Julia Kraft, Henry R. Kranzler, Kristi Krebs, Theodora Kunovac Kallak, Zoltán Kutalik, Elisa Lahtela, Marilyn Lake, Margit Hørup Larsen, Eric J. Lenze, Melissa Lewins, Glyn Lewis, Liming Li, Bochao Danae Lin, Kuang Lin, Penelope A. Lind, Yu-Li Liu, Donald J. MacIntyre, Dean F. MacKinnon, Brion S. Maher, Wolfgang Maier, Victoria S. Marshe, Gabriela A. Martinez-Levy, Koichi Matsuda, Hamdi Mbarek, Peter McGuffin, Sarah E. Medland, Susanne Meinert, Christina Mikkelsen, Susan Mikkelsen, Yuri Milaneschi, Iona Y. Millwood, Esther Molina, Francis M. Mondimore, Preben Bo Mortensen, Benoit H. Mulsant, Joonas Naamanka, Jake M. Najman, Matthias Nauck, Igor Nenadić, Kasper R. Nielsen, Ilja M. Nolt, Merete Nordentoft, Markus M. Nöthen, Mette Nyegaard, Michael C. O'Donovan, Asmundur Oddsson, Adrielle M. Oliveira, Catherine M. Olsen, Hogni Oskarsson, Sisse Rye Ostrowski, Michael J. Owen, Richard Packer, Teemu Palviainen, Pedro M. Pan, Carlos N. Pato, Michele T. Pato, Nancy L. Pedersen, Ole Birger Pedersen, Wouter J. Peyrot, James B. Potash, Martin Preisig, Michael H. Preuss, Jorge A. Quiroz, Miguel E. Renteria, Charles F. Reynolds III, John P. Rice, Saori Sakaue, Marcos L. Santoro, Robert A. Schoevers, Andrew Schork, Thomas G. Schulze, Tabea S. Send, Jianxin Shi, Engilbert Sigurdsson, Kritika Singh, Grant C.B. Sinnamon, Lea Sirignano, Olav B. Smeland, Daniel J. Smith, Tamar Sofer, Erik Sørensen, Sundararajan Srinivasan, Hreinn Stefansson, Kari Stefansson, Peter Straub, Mei-Hsin Su, André Tadic, Henning Teismann, Alexander Teumer, Anita Thapar, Pippa A. Thomson, Lise Wegner Thørner, Apostolia Topaloudi, Shih-Jen Tsai, Ioanna Tzoulaki, George Uhl, André G. Uitterlinden, Henrik Ullum, Daniel Umbricht, Robert J. Ursano, Sandra Van der Auwera, Albert M. van Hemert, Abirami Veluchamy, Alexander Viktorin, Henry Völzke, G. Bragi Walters, Xiaotong Wang, Agaz Wani, Myrna M. Weissman, Jürgen Wellmann, David C. Whiteman, Derek Wildman, Gonneke Willemsen, Alexander T. Williams, Bendik S. Winsvold, Stephanie H. Witt, Ying Xiong, Lea Zillich, John-Anker Zwart,  Twenty-Three and Me Research Team,  China Kadoorie Biobank Collaborative Group,  Estonian Biobank Research Team,  Genes & Health Research Team,  HUNT All-In Psychiatry,  The BioBank Japan Project,  VA Million Veteran Program, Ole A. Andreassen, Bernhard T. Baune, Klaus Berger, Dorret I. Boomsma, Anders D. Børglum, Gerome Breen, Na Cai, Hilary Coon, William E. Copeland, Byron Creese, Carlos S. Cruz-Fuentes, Darina Czamara, Lea K. Davis, Eske M. Derks, Enrico Domenici, Paul Elliott, Andreas J. Forstner, Micha Gawlik, Joel Gelernter, Hans J. Grabe, Steven P. Hamilton, Kristian Hveem, Catherine John, Jaakko Kaprio, Tilo Kircher, Marie-Odile Krebs, Po-Hsiu Kuo, Mikael Landén, Kelli Lehto, Douglas F. Levinson, Qingqin S. Li, Klaus Lieb, Ruth J.F. Loos, Yi Lu, Susanne Lucae, Jurjen J. Luykx, Hermine H.M. Maes, Patrik K. Magnusson, Hilary C. Martin, Nicholas G. Martin, Andrew McQuillin, Christel M. Middeldorp, Lili Milani, Ole Mors, Daniel J. Müller, Bertram Müller-Myhsok, Yukinori Okada, Albertine J. Oldehinkel, Sara A. Paciga, Colin N.A. Palmer, Peristera Paschou, Brenda W.J.H. Penninx, Roy H. Perlis, Roseann E. Peterson, Giorgio Pistis, Renato Polimanti, David J. Porteous, Danielle Posthuma, Jill A. Rabinowitz, Ted Reichborn-Kjennerud, Andreas Reif, Frances Rice, Roland Ricken, Marcella Rietschel, Margarita Rivera, Christian Rück, Giovanni A. Salum, Catherine Schaefer, Srijan Sen, Alessandro Serretti, Alkistis Skalkidou, Jordan W. Smoller, Dan J. Stein, Frederike Stein, Murray B. Stein, Patrick F. Sullivan, Martin Tesli, Thorgeir E. Thorgeirsson, Henning Tiemeier, Nicholas J. Timpson, Monica Uddin, Rudolf Uher, David A. van Heel, Karin J.H. Verweij, Robin G. Walters, Sylvia Wassertheil-Smoller, Jens R. Wendland, Thomas Werge, Aeilko H. Zwinderman, Karoline Kuchenbaecker, Naomi R. Wray, Stephan Ripke, Cathryn M. Lewis, Andrew M. McIntosh, Cell, online 14 January 2025, doi 10.1016/j.cell.2024.12.002.