Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways
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. , Logue Mark W. , 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 , Gelernter Joel , Geuze Elbert , Gillespie Charles , Goci Uka Aferdita , Gordon Scott D. , Guffanti Guia , Hammamieh Rasha , Harnal Supriya , Hauser Michael A. , Heath Andrew C. , Hemmings Sian M.J. , Michael Hougaard David , Jakovljevic Miro , Jett Marti , Otto Johnson Eric , 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. , Phillip Morris Charles , 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. , Solovieff Nadia , Sponheim Scott R. , Stein Dan J. , 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 Keith A. , Young Ross McD. , Zhao Hongyu , Zoellner Lori A. , Liberzon Israel , Ressler Kerry J. , Haas Magali , Koenen Karestan C. 
Published: November 2018

AbstractPost-traumatic stress disorder (PTSD) is a common and debilitating disorder. The risk of PTSD following trauma is heritable, but robust common variants have yet to be identified by genome-wide association studies (GWAS). We have collected a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls. We first demonstrate significant genetic correlations across 60 PTSD cohorts to evaluate the comparability of these phenotypically heterogeneous studies. In this largest GWAS meta-analysis of PTSD to date we identify a total of 6 genome-wide significant loci, 4 in European and 2 in African-ancestry analyses. Follow-up analyses incorporated local ancestry and sex-specific effects, and functional studies. Along with other novel genes, a non-coding RNA (ncRNA) and a Parkinson’s Disease gene,PARK2, were associated with PTSD. Consistent with previous reports, SNP-based heritability estimates for PTSD range between 10-20%. Despite a significant shared liability between PTSD and major depressive disorder, we show evidence that some of our loci may be specific to PTSD. These results demonstrate the role of genetic variation contributing to the biology of differential risk for PTSD and the necessity of expanding GWAS beyond European ancestry.