International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestryspecific genetic risk loci

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. 



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Caroline M. Nievergelt, Adam X. Maihofer, Torsten Klengel, Elizabeth G. Atkinson, Chia-Yen Chen, Karmel W. Choi, Jonathan R.I. Coleman, Shareefa Dalvie, Laramie E. Duncan, Joel Gelernter, Daniel F. Levey, Mark W. Logue, Renato Polimanti, Allison C. Provost, Andrew Ratanatharathorn, Murray B. Stein, Katy Torres, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Søren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Dragan Babić, Marie Bækvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Anders D. Børglum, Bekh Bradley, Megan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, José M. Caldas- de- Almeida, Anders M. Dale, Mark J. Daly, Nikolaos P. Daskalakis, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Seth G. Disner, Katharina Domschke, Alma Dzubur-Kulenovic, Christopher R. Erbes, Alexandra Evans, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Bizu Gelaye, Elbert Geuze, Charles Gillespie, Aferdita Goci Uka, Scott D. Gordon, Guia Guffanti, Rasha Hammamieh, Supriya Harnal, Michael A. Hauser, Andrew C. Heath, Sian M.J. Hemmings, David Michael Hougaard, Miro Jakovljevic, Marti Jett, Eric Otto Johnson, Ian Jones, Tanja Jovanovic, Xue-Jun Qin, Angela G. Junglen, Karen-Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Henry R. Kranzler, William S. Kremen, Bruce R. Lawford, Lauren A.M. Lebois, Catrin E. Lewis, Sarah D. Linnstaedt, Adriana Lori, Bozo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Jessica Maples-Keller, Charles Marmar, Alicia R. Martin, Nicholas G. Martin, Douglas Maurer, Matig R. Mavissakalian, Alexander McFarlane, Regina E. McGlinchey, Katie A. McLaughlin, Samuel A. McLean, Sarah McLeay, Divya Mehta, William P. Milberg, Mark W. Miller, Rajendra A. Morey, Charles Phillip Morris, Ole Mors, Preben B. Mortensen, Benjamin M. Neale, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Meaghan O’Donnell, Holly K. Orcutt, Matthew S. Panizzon, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, John P. Rice, Stephan Ripke, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Ken Ruggiero, Ariane Rung, Bart P.F. Rutten, Nancy L. Saccone, Sixto E. Sanchez, Dick Schijven, Soraya Seedat, Antonia V. Seligowski, Julia S. Seng, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Jennifer S. Stevens, Jennifer A. Sumner, Martin H. Teicher, Wesley K. Thompson, Edward Trapido, Monica Uddin, Robert J. Ursano, Leigh Luella van den Heuvel, Miranda Van Hooff, Eric Vermetten, Christiaan H. Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Jonathan D. Wolff, Rachel Yehuda, Ross McD. Young, Keith A. Young, Hongyu Zhao, Lori A. Zoellner, Israel Liberzon, Kerry J. Ressler, Magali Haas & Karestan C. Koenen | 2019
In: Nature Communication ISSN (online) 2041-1723 | 10 | 4558
https://www.nature.com/articles/s41467-019-12576-w
Online verschenen 08/10/2019
Trefwoorden: 
African Americans, Africans, Cardiovascular Diseases, Comorbidity, Congenital Diseases, Depressive Disorders, Epigenetics, Ethnic Identity, European Americans, Europeans, Females, Genetics, Immunological Symptoms, Intergenerational Effects, Males, Meta Analysis, Methodology, Posttraumatic Stress Disorder, Predisposition, PTSD (en), Schizophrenia, Somatic Symptoms
Affiliatie auteur(s): 
ARQ National Psychotrauma Centre