Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways | bioRxiv

Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways | bioRxiv

Largest genome-wide association study for PTSD identifies genetic risk loci in European and African ancestries and implicates novel biological pathways

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, Mark W Logue, Allison Provost, Andrew Ratanatharathorn, Murray B Stein, Katy Torres, Allison E Aiello, Lynn M Almli, Ananda B Amstadter, Soren B Andersen, Ole A Andreassen, Paul A Arbisi, Allison E Ashley-Koch, S Bryn Austin, Esmina Avdibegovic, Dragan Babic, Marie Baekvad-Hansen, Dewleen G Baker, Jean C Beckham, Laura J Bierut, Jonathan I Bisson, Marco P Boks, Elizabeth A Bolger, Anders D Borglum, Bekh Bradley, Megan Brashear, Gerome Breen, Richard A Bryant, Angela C Bustamante, Jonas Bybjerg-Grauholm, Joseph R Calabrese, Jose M Caldas-de-Almeida, Anders M Dale, Mark J Daly, Nikolaos P Daskalakis, Jurgen 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, Joel Gelernter, Elbert Geuze, Charles Gillespie, Aferdita G Uka, Scott D Gordon, Guia Guffanti, Rasha Hammamieh, Supriya Harnal, Michael A Hauser, Andrew C Heath, Sian M.J Hemmings, David M Hougaard, Miro Jakovljevic, Marti Jett, Eric O 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 P 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, Nadia Solovieff, Scott R Sponheim, Dan J Stein, Jennifer A Sumner, Martin H Teicher, Wesley K Thompson, Edward Trapido, Monica Uddin, Robert J Ursano, Leigh L van den Heuvel, Miranda van Hooff, Eric Vermetten, Christiaan H Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A Williams, Douglas A Williamson, Sherry Winternitz, Christiane Wolf, Erika J Wolf, Jonathan D Wolff, Rachel Yehuda, Kieth A Young, Ross M Young, Hongyu Zhao, Lori Zoellner, Israel Liberzon, Kerry Ressler, Magali Haas, Karestan C Koenen

doi: https://doi.org/10.1101/458562

This article is a preprint and has not been peer-reviewed [what does this mean?].

Abstract

Post-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.