Psychological trauma and the genetic overlap between posttraumatic stress disorder and major depressive disorder

Last updated:

19 November 2025

Author(s):

Jessica Mundy, Christopher Hübel, Joel Gelernter, Daniel Levey, Robin M. Murray, Megan Skelton, Murray B. Stein, Adam X. Maihofer, Caroline M. Nievergelt, Dewlen G. Baker, Victoria B. Risborough, Joseph R. Calabrese, Sandro Galea, Dan J. Stein, Nastassja Koen, Shareefa Dalvie, Allison E. Aiello, Andrea L. Roberts, K. C. Koenen, Nadia Solovieff, Henry R. Kranzler, Hongyu Zhao, Joel Gelernter, Lindsay A. Farrer, Eric Otto Johnson, John P. Rice, Laura J. Bierut, Nancy L. Saccone, Alexander McFarlane, David Forbes, Derrick Silove, Meaghan O'Donnell, Richard A. Bryant, Miranda van Hooff, Scott R. Sponheim, Seth G. Disner, Robert H. Pietrzak, Chia-Yen Chen, Jordan W. Smoller, Murray B. Stein, Robert J. Ursano, Ronald C. Kessler, Angela G. Junglen, Douglas L. Delahanty, Ananda B. Amstadter, Christina M. Sheerin, Ken Ruggiero, Katie A. McLaughlin, Matthew Peverill, JM Caldas-de-Almeida, S. Bryn Austin, Bizu Gelaye, Michelle A. Williams, Sixto E. Sanchez, Carol E. Franz, Matthew S. Panizzon, Michael J. Lyons, William S. Kremen, Ole A. Andreassen, Anders M. Dale, Bart P. F. Rutten, Christiaan Vinkers, Dick Schijven, Elbert Geuze, Eric Vermetten, Jurjen J. Luykx, Marco P. Boks, Allison E. Ashley-Koch, Jean C. Beckham, Melanie E. Garrett, Michael A. Hauser, Michelle F. Dennis, Nathan A. Kimbrel, Xue-Jun Qin, Karen-Inge Karstoft, Soren B. Andersen, Anders D. Borglum, David Michael Hougaard, Jonas Bybjerg-Grauholm, Laramie E. Duncan, Marie Bµkvad-Hansen, Merete Nordentoft, Ole Mors, P. B. Mortensen, Thomas Werge, Wesley K. Thompson, Yunpeng Wang, Andrew C. Heath, Elliot C. Nelson, Nicholas G Martin, Scott D. Gordon, Erika J. Wolf, Mark W. Logue, Mark W. Miller, Regina E. McGlinchey, William Milberg, Christopher R. Erbes, Melissa A. Polusny, Paul A. Arbisi, Alan L. Peterson, Douglas E. Williamson, Keith A. Young, D. Maurer, Alex O. Rothbaum, Lori A. Zoellner, Matig R. Mavissakalian, Norah C. Feeny, P. Roy-Byrne, Barbara O. Rothbaum, Jessica Maples-Keller, Alaptagin Khan, Jonathan D. Wolff, Lauren A. M. Lebois, Martin H. Teicher, Milissa L. Kaufman, Sherry Winternitz, Elizabeth A. Bolger, Antonia V. Seligowski, Holly K. Orcutt, Alexandra Evans, Bozo Lugonja, Catrin Lewis, Ian Jones, Jonathan I. Bisson, Samuel A. McLean, Sarah D. Linnstaedt, Edward S. Peters, Ariane Rung, Edward Trapido, Megan Brashear, Adriana Lori, Alicia K. Smith, Bekh Bradley, Charles Gillespie, Guia Guffanti, Kerry J. Ressler, Lynn M. Almli, Tanja Jovanovic, Angela C. Bustamante, Monica Uddin, Leigh Luella van den Heuvel, S. Seedat, S. M. J Hemmings, Aferdita Goci Uka, Alma Dzubur Kulenovic, Christiane Wolf, Dragan Babic, Esmina Avdibegovic, Jürgen Deckert, Katharina Domschke, Miro Jakovljevic, Charles Marmar, Janine D. Flory, Marti Jett, Rachel Yehuda, Rasha Hammamieh, Anthony P. King, Israel Liberzon, Julia S. Seng, Charles Phillip Morris, Divya Mehta, Joanne Voisey, B. R. Lawford, Ross McD. Young, Sarah McLeay, Nikolaos P. Daskalakis, Sonya B. Norman, Zhewu Wang, Gerome Breen, Jonathan R.I. Coleman, Torsten Klengel, Katy Torres, Karmel W. Choi, Daniel F Levey, Renato Polimanti, Elizabeth G. Atkinson, Alicia R. Martin, Benjamin M. Neale, Mark J. Daly, Stephan Ripke, Andrew Ratanatharathorn, Allison C. Provost, Magali Haas, Jennifer S. Stevens, Rajendra A. Morey, Supriya Harnal, Preben B. Mortensen, Soraya Seedat, Jennifer A. Sumner, Evangelos Vassos, Gerome Breen, Jonathan R. I. Coleman

Publish date:

4 June 2021

Journal:

Psychological Medicine

PubMed ID:

34085609

DOI:

10.1017/s0033291721000830

Abstract

BACKGROUND: Posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) are commonly reported co-occurring mental health consequences of psychological trauma exposure. The disorders have high genetic overlap. Trauma is a complex phenotype but research suggests that trauma sensitivity has a heritable basis. We investigated whether sensitivity to trauma in those with MDD reflects a similar genetic component in those with PTSD.

METHODS: Genetic correlations between PTSD and MDD in individuals reporting trauma and MDD in individuals not reporting trauma were estimated, as well as with recurrent MDD and single-episode MDD, using genome-wide association study (GWAS) summary statistics. Genetic correlations were replicated using PTSD data from the Psychiatric Genomics Consortium and the Million Veteran Program. Polygenic risk scores were generated in UK Biobank participants who met the criteria for lifetime MDD (N = 29 471). We investigated whether genetic loading for PTSD was associated with reporting trauma in these individuals.

RESULTS: Genetic loading for PTSD was significantly associated with reporting trauma in individuals with MDD [OR 1.04 (95% CI 1.01-1.07), Empirical-p = 0.02]. PTSD was significantly more genetically correlated with recurrent MDD than with MDD in individuals not reporting trauma (rg differences = ~0.2, p < 0.008). Participants who had experienced recurrent MDD reported significantly higher rates of trauma than participants who had experienced single-episode MDD (χ2 > 166, p < 0.001).

CONCLUSIONS: Our findings point towards the existence of genetic variants associated with trauma sensitivity that might be shared between PTSD and MDD, although replication with better powered GWAS is needed. Our findings corroborate previous research highlighting trauma exposure as a key risk factor for recurrent MDD.