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

AbstractThe 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.